Immunopathology

1.
Vet Immunol Immunopathol. 2019 Dec 16;220:109996. doi: 10.1016/j.vetimm.2019.109996. [Epub ahead of print]
Identification of the JAK-STAT pathway in canine splenic hemangiosarcoma, thyroid carcinoma, mast cell tumor, and anal sac adenocarcinoma.
Cletzer E1, Klahn S2, Dervisis N1, LeRoith T3.

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Abstract


Dysregulation of the Janus Kinase (JAK) - Signal Transducer and Activator of Transcription (STAT) cellular signaling pathway has been associated with the development and progression of multiple human cancers. STAT3 has been reported to be present and constitutively active in a number of veterinary cancers, and few studies have reported mutations or activation of JAK1 or JAK2. Archived tissue samples from 54 client-owned dogs with histologically-diagnosed HSA, MCT, TC, or AGASACA were evaluated by immunohistochemical scoring of JAK1, JAK2, STAT3, and the phosphorylated counterparts pJAK1, pJAK2, and pSTAT3. IHC scoring was retrospectively analyzed with retrospectively-collected clinical parameters, including patient characteristics, metastasis, and survival. JAK1, pJAK1, JAK2, pJAK2, STAT3, and pSTAT3 were present in all tumor types evaluated. Significant correlations between JAK 1/2 or STAT3 and activated or downstream components were identified in all tumor types. Clinically, pSTAT3 was correlated with development of metastasis in dogs with MCT, while increased JAK1 expression or activation may impact survival in dogs with MCT or HSA. These findings provide a foundation to further investigate the JAK-STAT pathway in canine malignancies for additional therapeutic options.

Copyright © 2019 Elsevier B.V. All rights reserved.

KEYWORDS:

Cancer; Dog; Immunohistochemistry; JAK1; JAK2; STAT3
PMID: 31958674 DOI: 10.1016/j.vetimm.2019.109996

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Select item 319586332.
J Steroid Biochem Mol Biol. 2020 Jan 17:105600. doi: 10.1016/j.jsbmb.2020.105600. [Epub ahead of print]
VDR in Salivary Gland Homeostasis and Cancer.
DeSantis KA1, Robilotto SL1, Matson M1, Kotb NM2, Lapierre CM3, Minhas Z3, Leder AA3, Abdul K3, Facteau EM3, Welsh J4.

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Abstract


The vitamin D receptor (VDR) and its ligand 1,25(OH)2D3 (1,25D) impact differentiation and exert anti-tumor effects in many tissues, but its role in salivary gland has yet to be defined. Using immunohistochemistry (IHC), we have detected strong VDR expression in murine and human salivary gland ducts. Compared to normal gland, VDR protein expression was retained in differentiated human pleomorphic adenoma (PA) but was undetectable in undifferentiated PA and in carcinomas, suggesting deregulation of VDR during salivary cancer progression. To gain insight into the potential role of VDR in salivary cancer, we assessed the effects of vitamin D in vivo and in vitro. Despite the presence of VDR in salivary gland, chronic dietary vitamin D restriction did not alter morphology of the salivary epithelium in C57/Bl6 mice. The localization of VDR in ductal epithelium prompted us to examine the effects of 1,25D in an established cell line (mSGc) derived from normal murine submandibular gland (SMG). This previously characterized cell line consists of multiple stem, progenitor and differentiated cell types as determined by mutually exclusive cellular expression of basal, ductal and myoepithelial markers. We demonstrated VDR expression and regulation of VDR target genes Vdr and Postn by 1,25D in mSGc, indicating functional ligand-mediated transcriptional activity. The effect of VDR signaling on epithelial differentiation markers was assessed by qPCR and IHC in mSGc cells treated with 1,25D. We found that 1,25D reduced mRNA expression of the basal cell progenitor marker keratin 5 (K5) and increased expression of the differentiated ductal cell marker keratin 7 (K7). Further, we found that 1,25D significantly decreased the number of proliferating cells, including proliferating K5+ cells. Characterization of cell cycle by Muse cytometry indicated 1,25D treatment decreased cells in S, G2, and M phase. The inhibition of K5+ cell proliferation by 1,25D is of particular interest because K5+ basal cells contribute to a wide variety of salivary tumor types. Our studies suggest that 1,25D alters cancer-relevant progenitor and differentiation markers in the salivary gland.

Copyright © 2020. Published by Elsevier Ltd.

KEYWORDS:

VDR; Vitamin D; cancer; salivary gland
PMID: 31958633 DOI: 10.1016/j.jsbmb.2020.105600

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Select item 319583813.
Arch Pathol Lab Med. 2020 Jan 20. doi: 10.5858/arpa.2019-0473-RA. [Epub ahead of print]
Pancreatic Solid Pseudopapillary Neoplasm: Key Pathologic and Genetic Features.
La Rosa S1, Bongiovanni M1.

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Abstract

CONTEXT.—:

Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor generally associated with a good prognosis. Solid pseudopapillary neoplasms show peculiar morphologic features, but sometimes the differential diagnosis with other pancreatic neoplasms (ie, pancreatic neuroendocrine tumors) can be a challenging task, especially in cytologic or biopsy specimens. In these cases immunohistochemistry is a useful tool, but the diagnostic utility of several proposed immunohistochemical markers is questionable. In recent years, despite several attempts to characterize the pathogenetic, molecular, and prognostic features of solid pseudopapillary neoplasms, they still remain unclear.
OBJECTIVE.—:

To give the reader a comprehensive update on this entity.
DATA SOURCES.—:

The PubMed database (US National Library of Medicine) was searched using the following string: pseudopapillary tumor [AND/OR] neoplasm [AND/OR] pancreas. All articles written in English were included. In addition, because a heterogeneous terminology has been used in the past to define solid pseudopapillary neoplasms, the reference lists of each paper selected in the PubMed database were also reviewed.
CONCLUSIONS.—:

This review gives a comprehensive update on the pathologic, clinical, and molecular features of SPNs, particularly addressing issues and challenges related to diagnosis. In addition, we have tried to correlate the molecular alterations with the morphologic and clinical features.
PMID: 31958381 DOI: 10.5858/arpa.2019-0473-RA

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Select item 319580764.
Cancer Biomark. 2020 Jan 6. doi: 10.3233/CBM-190739. [Epub ahead of print]
Knockdown of annexin VII enhances nasopharyngeal carcinoma cell radiosensitivity in vivo and in vitro.
Gui SJ, Ding RL, Wan YP, Zhou L, Chen XJ, Zeng GQ.

Abstract

BACKGROUND:

Radioresistance leads to treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, enhancing the radiosensitivity of NPC cells would likely increase the effectiveness of radiotherapy. Annexin VII (Annexin A7, ANXA7) might be a tumor promoter in NPC but its functions in radiosensitivity remain unclear.
METHODS:

NPC cell lines CNE2-shANXA7 and CNE2-pLKO.1 were generated and CNE2-shANXA7 nude mice xenograft tumor models were established. The main effects and molecular mechanisms of ANXA7 knockdown in NPC radiosensitivity were studied in vitro and in vivo by analyzing cell viability, clonogenicity, apoptosis, cell cycle distribution, tumor radioresponse and immunohistochemistry assay.
RESULTS:

ANXA7 knockdown revealed potentially enhanced NPC cell radiosensitivity via apoptosis and increased the cell number at the G2/M phase. In the xenograft model, NPC cells with ANXA7 knockdown were dramatically sensitive to irradiation and tumor growth was significantly suppressed. Compared to CNE2-pLKO.1 xenografts, CNE2-shANXA7 showed more γ-H2AX foci and less phospho-DNA PKcs.
CONCLUSIONS:

ANXA7 knockdown increased the radiosensitivity of NPC by enhancing apoptosis, modulating the cell cycle distribution into more radiosensitive phases, promoting DNA damage, and inhibiting repair. We showed that decreased ANXA7 levels enhanced radiosensitivity and provided insights into the therapeutic targets for NPC radiotherapy.

KEYWORDS:

Nasopharyngeal carcinoma; annexin VII; radiosensitivity
PMID: 31958076 DOI: 10.3233/CBM-190739

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Select item 319572505.
Asia Pac J Clin Oncol. 2020 Jan 19. doi: 10.1111/ajco.13302. [Epub ahead of print]
Correlations between CD4+ FoxP3+ Treg and expression of FoxM1 and Ki-67 in gastric cancer patients.
Ma K1, Li X2, Lv J2, Liu Z2, Zhang L2, Cong H2, Wang H2, Shen F2, Yue L3.

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Abstract

AIMS:

In this study, we intended to analyze the clinical significance of CD4+ FoxP3+ Tregs in gastric cancer patients and investigate the relationship between the proportion of CD4+ FoxP3+ Tregs in the peripheral blood and the expression of FoxM1 and Ki-67 in gastric cancer tissues.
METHODS:

Flow cytometry was used to measure the CD4+ FoxP3+ Tregs level in peripheral blood from 70 gastric cancer patients one day before gastrectomy and D2 lymph node dissection. Immunohistochemistry staining was used to detect the expression of FoxM1 and Ki-67 in gastric cancer tissues. Data on clinico-pathological features and correlation between Tregs and the expression of FoxM1 and Ki-67 were then analyzed.
RESULTS:

The average proportion of CD4+ FoxP3+ Tregs in gastric cancer patients' peripheral blood before surgery was 10.12 ± 2.85%, which was significantly higher in patients with late AJCC stage (P = 0.029) or lymph node metastasis (P = 0.003) compared to patients at earlier AJCC stage or without lymph node metastasis. The levels of CD4+ FoxP3+ Treg cells was positively correlated with the protein expression of FoxM1 (P = 0.003) and Ki-67 (P = 0.001), respectively.
CONCLUSION:

These results suggest the level of CD4+ FoxP3+ Treg cells in peripheral blood has clinical significance in gastric cancer patients. The overexpression of FoxM1 and Ki-67 may relate to immunosuppression in gastric cancer.

© 2020 John Wiley & Sons Australia, Ltd.

KEYWORDS:

FoxM1; Ki-67; Tregs; gastric cancer
PMID: 31957250 DOI: 10.1111/ajco.13302

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Select item 319571766.
Oral Dis. 2020 Jan 19. doi: 10.1111/odi.13282. [Epub ahead of print]
Silencing of FOXA2 decreases E-cadherin expression and is associated with lymph node metastasis in oral cancer.
Bow YD1, Wang YY2,3, Chen YK2,3,4,5, Su CW3,6, Hsu CW3,6, Xiao LY3, Yuan SS3,7,8,9,10, Li RN1.

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Abstract

OBJECTIVES:

FOXA2 gene methylation links to the progression of cancers, but has not been documented in oral cancer. Herein, we explore the role of FOXA2 in the migration of oral cancer cells.
MATERIAL AND METHODS:

Methylation-specific PCR was applied for gene methylation. Wound healing and transwell experiments were tested for cell migration. FOXA2 expression in oral cancer tissues was addressed by immunohistochemistry, followed by statistical analysis of its association with clinical manifestations and patient survival.
RESULTS:

FOXA2 bound to the promoter of CDH1 and enhanced the expression of its gene product E-cadherin, and decreased the cancer cell migration activity. High FOXA2 expression in oral cancer tissues was associated with high E-cadherin expression, decreased lymph node metastasis, and increased patient survival.
CONCLUSION:

FOXA2-E-cadherin link is involved in regulation of oral cancer cell metastasis and provides a new insight for the tumor suppressor activity of FOXA2 in oral cancer.

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

KEYWORDS:

E-cadherin; FOXA2; cell migration; gene methylation; oral cancer
PMID: 31957176 DOI: 10.1111/odi.13282

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Select item 319569627.
Protein Cell. 2020 Jan 19. doi: 10.1007/s13238-019-00687-5. [Epub ahead of print]
Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis.
Jiang HY1,2, Najmeh S1,2, Martel G3, MacFadden-Murphy E3, Farias R3, Savage P4, Leone A1,2, Roussel L3, Cools-Lartigue J1,2, Gowing S1,2, Berube J3, Giannias B1, Bourdeau F1, Chan CHF5, Spicer JD1,2, McClure R6, Park M4, Rousseau S3, Ferri LE7,8.

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Abstract


While emerging data suggest nucleotide oligomerization domain receptor 1 (NOD1), a cytoplasmic pattern recognition receptor, may play an important and complementary role in the immune response to bacterial infection, its role in cancer metastasis is entirely unknown. Hence, we sought to determine the effects of NOD1 on metastasis. NOD1 expression in paired human primary colon cancer, human and murine colon cancer cells were determined using immunohistochemistry and immunoblotting (WB). Clinical significance of NOD1 was assessed using TCGA survival data. A series of in vitro and in vivo functional assays, including adhesion, migration, and metastasis, was conducted to assess the effect of NOD1. C12-iE-DAP, a highly selective NOD1 ligand derived from gram-negative bacteria, was used to activate NOD1. ML130, a specific NOD1 inhibitor, was used to block C12-iE-DAP stimulation. Stable knockdown (KD) of NOD1 in human colon cancer cells (HT29) was constructed with shRNA lentiviral transduction and the functional assays were thus repeated. Lastly, the predominant signaling pathway of NOD1-activation was identified using WB and functional assays in the presence of specific kinase inhibitors. Our data demonstrate that NOD1 is highly expressed in human colorectal cancer (CRC) and human and murine CRC cell lines. Clinically, we demonstrate that this increased NOD1 expression negatively impacts survival in patients with CRC. Subsequently, we identify NOD1 activation by C12-iE-DAP augments CRC cell adhesion, migration and metastasis. These effects are predominantly mediated via the p38 mitogen activated protein kinase (MAPK) pathway. This is the first study implicating NOD1 in cancer metastasis, and thus identifying this receptor as a putative therapeutic target.

KEYWORDS:

ML130; NOD1; cancer migration; cancer-extracellular matrix adhesion; colon cancer; iE-DAP; intravital microscopy; metastasis; p38 MAPK activation; survival analysis
PMID: 31956962 DOI: 10.1007/s13238-019-00687-5

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Select item 319563638.
J Cancer. 2020 Jan 1;11(5):1170-1181. doi: 10.7150/jca.37147. eCollection 2020.
Up-regulation of peroxiredoxin-1 promotes cell proliferation and metastasis and inhibits apoptosis in cervical cancer.
Lu E1, Hu X1, Pan C1, Chen J1, Xu Y1, Zhu X1.

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Abstract


Objective: To investigate the effect of peroxiredoxin 1 (PRDX1) on the biological behavior of cervical cancer cells and the possible mechanism. Materials and methods: The expression of PRDX1 in human cervical cancer tissues and adjacent non-tumor tissues were detected by immunohistochemistry (IHC). Lentivirus containing PRDX1-cDNA or shRNA against PRDX1 was constructed to overexpress or knockdown PRDX1 in SiHa cervical cancer cells. Cell proliferation was tested by CCK-8 and BrdU incorporation assay and cell apoptosis was evaluated by AnnexinV-PE /7AAD assay. Scratch wound and transwell invasion assay were used to test migration and invasion activity after PRDX1 was overexpressed or suppressed. Furthermore, the effect of PRDX1 on cell proliferation and apoptosis was also studied using a xenograft model of nude mice. Results: The expression of PRDX1 protein was significantly up-regulated in the tumor tissues compared with the paired adjacent non-tumor tissues. Meanwhile, PRDX1 overexpression was associated with tumor stage, lymphatic metastasis and differentiation. Overexpression of PRDX1 significantly promoted proliferation and inhibited apoptosis by increasing the expression of Nanog, proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (Bcl-2) and downregulating the expression of Bcl2-associated X protein (BAX) in SiHa cervical cancer cells. Moreover, PRDX1 overexpression increased invasion and migration of SiHa cervical cancer cells via up-regulating the expression of Snail and matrix metalloprotein 9 (MMP-9) and down-regulating the expression of E-cadherin. Knockdown of PRDX1 resulted in the opposite results. The role of PRDX1 in promoting SiHa cervical cancer cell proliferation and inhibiting apoptosis has also been confirmed in vivo in a mouse xenograft model. Conclusions: PRDX1 promoted cell proliferation, migration, and invasion and suppressed apoptosis of cervical cancer possibly via regulating the expression of related protein.

© The author(s).

KEYWORDS:

PRDX1; apoptosis; cervical cancer; invasion; migration; proliferation
PMID: 31956363 PMCID: PMC6959069 DOI: 10.7150/jca.37147
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Select item 319563499.
J Cancer. 2020 Jan 1;11(5):1027-1037. doi: 10.7150/jca.37401. eCollection 2020.
Phosphoribosyl pyrophosphate synthetases 2 knockdown inhibits prostate cancer progression by suppressing cell cycle and inducing cell apoptosis.
Qiao H1, Tan X2, Lv DJ3,2, Xing RW4, Shu FP2, Zhong CF2, Li C1, Zou YG5, Mao XM3,2.

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Abstract


Phosphoribosyl pyrophosphate synthetases 2 (PRPS2) protein function as nucleotide synthesis enzyme that plays vital roles in cancer biology. However, the expression profile and function of PRPS2 in prostate cancer (PCa) remain to be identified. Here we investigated the expression of PRPS2 protein in human PCa and paired normal tissues by immunohistochemistry, meanwhile the regulatory effects on cell proliferation, apoptosis and growth of xenograft tumors in nude mice were evaluated in PCa cells with PRPS2 depletion. Moreover, the signaling pathways were also explored by western blot analysis and quantitative polymerase chain reaction assays. We found that PRPS2 was dramatically upregulated in prostate adenocarcinoma tissues in comparison with normal tissues, and that increased PRPS2 was linked intimately to advanced clinical stage and pT status. Functional experiments showed that knockdown of PRPS2 significantly suppressed cell growth both in vitro and in vivo. In addition, depletion of PRPS2 induced G1 phase cell cycle arrest and elevated cell apoptosis. Silencing of PRPS2 resulted in the decreased expression of Bcl‑2 and cyclinD1 and increased levels of Bax, cleavage of caspases‑3, caspases‑9 and PARP. Furthermore, we also detected PRPS2 expression was significantly induced after DHT treatment, which implied the important role of PRPS2 in oncogenesis of PCa. Taken together, our findings elucidated that PRPS2 may be a potential novel candidate for PCa therapy.

© The author(s).

KEYWORDS:

Phosphoribosyl pyrophosphate synthetase 2; apoptosis; proliferation; prostate cancer.
PMID: 31956349 PMCID: PMC6959080 DOI: 10.7150/jca.37401
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Select item 3195600310.
J Vasc Interv Radiol. 2020 Jan 16. pii: S1051-0443(19)30905-4. doi: 10.1016/j.jvir.2019.10.015. [Epub ahead of print]
High-Frequency Irreversible Electroporation for Treatment of Primary Liver Cancer: A Proof-of-Principle Study in Canine Hepatocellular Carcinoma.
Partridge BR1, O'Brien TJ2, Lorenzo MF2, Coutermarsh-Ott SL3, Barry SL1, Stadler K1, Muro N1, Meyerhoeffer M1, Allen IC1, Davalos RV2, Dervisis NG4.

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Abstract

PURPOSE:

To determine the safety and feasibility of percutaneous high-frequency irreversible electroporation (HFIRE) for primary liver cancer and evaluate the HFIRE-induced local immune response.
MATERIALS AND METHODS:

HFIRE therapy was delivered percutaneously in 3 canine patients with resectable hepatocellular carcinoma (HCC) in the absence of intraoperative paralytic agents or cardiac synchronization. Pre- and post-HFIRE biopsy samples were processed with histopathology and immunohistochemistry for CD3, CD4, CD8, and CD79a. Blood was collected on days 0, 2, and 4 for complete blood count and chemistry. Numeric models were developed to determine the treatment-specific lethal thresholds for malignant canine liver tissue and healthy porcine liver tissue.
RESULTS:

HFIRE resulted in predictable ablation volumes as assessed by posttreatment CT. No detectable cardiac interference and minimal muscle contraction occurred during HFIRE. No clinically significant adverse events occurred secondary to HFIRE. Microscopically, a well-defined ablation zone surrounded by a reactive zone was evident in the majority of samples. This zone was composed primarily of maturing collagen interspersed with CD3+/CD4-/CD8- lymphocytes in a proinflammatory microenvironment. The average ablation volumes for the canine HCC patients and the healthy porcine tissue were 3.89 cm3 ± 0.74 and 1.56 cm3 ± 0.16, respectively (P = .03), and the respective average lethal thresholds were 710 V/cm ± 28.2 and 957 V/cm ± 24.4 V/cm (P = .0004).
CONCLUSIONS:

HFIRE can safely and effectively be delivered percutaneously, results in a predictable ablation volume, and is associated with lymphocytic tumor infiltration. This is the first step toward the use of HFIRE for treatment of unresectable liver tumors.

Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.
PMID: 31956003 DOI: 10.1016/j.jvir.2019.10.015

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Select item 3195591011.
Acta Histochem. 2020 Jan 16:151505. doi: 10.1016/j.acthis.2020.151505. [Epub ahead of print]
Utility of the immunohistochemical analysis of DNA mismatch-repair proteins in endometrial hyperplasia.
Missaoui N1, Boukhari N2, Limam S2, Hmissa S3, Mokni M2.

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Abstract


The utility of the expression lack of DNA mismatch-repair (MMR) proteins in the detection of Lynch syndrome in endometrial hyperplasia as precursor lesion of endometrial carcinoma has not been well-established. The study investigated the immunoexpression pattern of MMR proteins in endometrial hyperplasia from Tunisian patients. We carried out a retrospective study of 60 endometrial hyperplasias diagnosed among Tunisian patients. Expression of MLH1, MSH2, MSH6, and PMS2 proteins was performed by immunohistochemistry on whole-slide sections of archival tissues. Analysis of MLH1 promoter methylation and microsatellite alterations was conducted in appropriate cases. Microsatellite instability screening was assessed using the Bethesda panel, including BAT25, BAT26, D17S250, D2S123, and D5S346 markers. Expression of MMR proteins was observed in all hyperplasias without atypia as well as in 27 out of 29 atypical hyperplasias. Only two atypical hyperplasias exhibited expression loss of MMR proteins. A single case revealed MSH6 expression lack. Expression loss of MLH1 and PMS2 was identified in another atypical hyperplasia and was associated with hypermethylation of MLH1 promoter. This patient had no familial history of endometrial cancer at the diagnostic time. The two deficient MMR cases showed microsatellite stable pattern. In conclusion, only two endometrial hyperplasias displayed an altered pattern of MMR expression. Our results suggest the limited utility of the immunohistochemical analysis of MMR protein in the early detection of Lynch syndrome in Tunisian patients diagnosed with endometrial hyperplasias. Multicenter studies with larger sample size are needed to more explore these findings.

Copyright © 2020 Elsevier GmbH. All rights reserved.

KEYWORDS:

Endometrium; Hyperplasia; Immunohistochemistry; Lynch syndrome; MMR protein; Microsatellite instability
PMID: 31955910 DOI: 10.1016/j.acthis.2020.151505

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Select item 3195580312.
J Comp Pathol. 2020 Jan;174:54-57. doi: 10.1016/j.jcpa.2019.10.190. Epub 2019 Nov 30.
Meningeal Granular Cell Tumour in a Green Tree Python (Morelia viridis).
Finnegan DK1, Cartoceti AN2, Hauck AM1, LaDouceur EEB3.

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Abstract


Granular cell tumours (GCTs) are uncommon neoplasms mostly reported in man, dogs and horses. The origin of GCT is thought to be Schwann cells, with the associated characteristics of neural crest morphology. Neoplastic cells often demonstrate positive immunoreactivity for S100, LC3, vimentin and p62. They are also periodic acid-Schiff (PAS) positive and diastase resistant. A female green tree python (Morelia viridis) was presented for severe constipation and hyporexia of 4 month's duration and, despite treatment, died the next day. A 4.8 × 3.4 mm intracalvarial GCT was identified, compressing the overlying cerebrum without invasion. Neoplastic cells were immunoreactive to S100 and had brightly eosinophilic cytoplasmic granules that were PAS positive and diastase resistant. Electron microscopy revealed numerous cytoplasmic lysosomes in neoplastic cells. GCTs are reported rarely in non-mammalian species with three reports in birds. This represents the first report of a GCT in a reptile.

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS:

granular cell tumour; green tree python; immunohistochemistry; transmission electron microscopy
PMID: 31955803 DOI: 10.1016/j.jcpa.2019.10.190

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Select item 3137516113.
J Comp Pathol. 2019 Jul;170:70-73. doi: 10.1016/j.jcpa.2019.05.009. Epub 2019 Jun 22.
Renin-producing Tumour in the Kidney of a Cat.
Brown P1, Stallwood J2, Costa M2, Bruneval P3.

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Abstract


Clinical and post-mortem examination of an adult neutered male cat with immune-mediated haemolytic anaemia revealed suspected nodules of tumour tissue in the cortex of the right kidney. Cytology and histopathology indicated a malignant renal tumour of undetermined type. Immunohistochemistry confirmed renin production by a proportion of the tumour cells. The lesion may represent a renal adenocarcinoma producing renin or a tumour of juxtaglomerular cells ('reninoma').

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS:

cat; kidney; renin; tumour
PMID: 31375161 DOI: 10.1016/j.jcpa.2019.05.009
[Indexed for MEDLINE]
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Select item 3137516014.
J Comp Pathol. 2019 Jul;170:60-69. doi: 10.1016/j.jcpa.2019.05.008. Epub 2019 Jun 22.
Significance of Angiogenic Growth Factors in Bovine Ocular Squamous Cell Carcinoma.
Sözmen M1, Devrim AK2, Sudağıdan M3, Kabak YB4, Beytut E5, Özba B6.

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Abstract


Bovine ocular squamous cell carcinoma (BOSCC) is the most common and economically significant neoplasm of the eye in cattle. This study investigated the role of angiogenic growth factors in the pathogenesis of BOSCC. Eighteen cases of BOSCC were classified histopathologically according to the degree of differentiation. Normal upper and lower eyelids and third eyelids collected from the right and left eyes of six healthy cattle aged 1-3 years, that had been presented for slaughter to abattoirs, served as controls. Transcription of genes encoding the angiogenic growth factors vascular endothelial growth factor-C (VEGF-C), basic fibroblast growth factor (bFGF), platelet-derived growth factor-C (PDGF-C) and platelet-derived growth factor receptor-α (PDGFR-α) was determined by quantitative real-time polymerase chain reaction (RT-PCR) in tissue obtained from paraffin wax blocks. Immunohistochemistry (IHC) was utilized to detect intensity of expression and tissue distribution of these growth factors. IHC results revealed that bFGF and PDGF-C were elevated significantly (P >0.05) and VEGF-C expression was decreased in BOSCC compared with healthy control tissue. PDGR-α expression was elevated; however, the difference, compared with control tissues, was not significant. RT-PCR results showed an inverse relationship to the results of IHC; where protein levels were elevated their corresponding mRNA levels were decreased or vice-versa. Angiogenic regulators therefore appear to play a role in the pathogenesis of BOSCC.

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS:

cattle; gene expression; immunohistochemistry; squamous cell carcinoma
PMID: 31375160 DOI: 10.1016/j.jcpa.2019.05.008
[Indexed for MEDLINE]
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MeSH terms, Substance


Select item 3137515615.
J Comp Pathol. 2019 Jul;170:26-33. doi: 10.1016/j.jcpa.2019.05.005. Epub 2019 Jun 12.
Expression of Oxytocin Receptors in Canine Mammary Tumours.
Benavente MA1, Bianchi CP2, Aba MA2.

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Abstract


The aims of the present study were: (1) to investigate the presence of oxytocin receptors in benign and malignant canine mammary tumours (CMTs) and to evaluate the possible association between oxytocin receptor (OTR) expression and the expression of oestrogen receptor (OR) α and ORβ, and (2) to examine associations between receptor expression and tumour size, clinical stage, histological subtype, tumour grading and lymph node status. Forty-three canine mammary tumour samples (19 benign, 24 malignant) were examined by immunohistochemistry to detect OTR, ORα and ORβ expression. Results were expressed as total score for each receptor, calculated as the sum of the percentage of positive cells and the intensity of immunolabelling. In all of the evaluated mammary tumour samples, OTRs were identified and their expression tended to be higher in benign tumours than malignant tumours. Among the malignant tumours, the expression of OTR was significantly higher in grade I and II lesions than in grade III lesions. ORα-positive tumours had a tendency towards a higher OTR total score than ORα-negative tumours. These results report for the first time that CMTs express OTRs and their expression is associated with the presence of ORα. An interaction between oxytocin and the OTR might play a role in the development and progression of this type of neoplasia.

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS:

dog; mammary tumour; oestrogen receptor; oxytocin receptor
PMID: 31375156 DOI: 10.1016/j.jcpa.2019.05.005
[Indexed for MEDLINE]
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MeSH terms, Substances


Select item 3137515216.
J Comp Pathol. 2019 Jul;170:10-21. doi: 10.1016/j.jcpa.2019.05.002. Epub 2019 Jun 7.
Feline Leukaemia Virus Associated with Leukaemia in Cats in Santa Catarina, Brazil.
Cristo TG1, Biezus G1, Noronha LF2, Gaspar T2, Dal Pont TP2, Withoeft JA2, Furlan LV2, Costa LS2, Traverso SD3, Casagrande RA4.

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Abstract


Leukaemia is a haemopoietic neoplasm originating from myeloid or lymphoid precursors in the bone marrow and may be either acute or chronic. These tumours are rare, but occur more frequently in cats because of an association with the feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV). To the best of our knowledge, no studies conducted in Brazil to date have analysed the association between leukaemia and FeLV and FIV infection in cats. The aim of this study was to perform a histopathological analysis of feline leukaemia and evaluate the association between leukaemia and FeLV and FIV infection in cats. The study evaluated 37 cats with leukaemia diagnosed between 2009 and 2017. The animals underwent necropsy examination, histopathology and immunohistochemistry with anti-FeLV gp70 and anti-FIV p24 gag antibodies. Of the evaluated animals, 54% (20/37) were males and 43.2% (16/37) were females. With respect to the life stage of the animals, 24.3% (9/37) were junior, 32.4% (12/37) were prime, 18.9% (7/37) were mature and 10.8% (4/37) were senior, and five animals were of unknown age. Myeloid leukaemia occurred in 56.8% (21/37) of the cases and lymphocytic leukaemia occurred in 43.2% (16/37) of the cases. Acute leukaemia (73%, 27/37) was more common than chronic leukaemia (27%, 10/37). The positivity for FeLV (78.4%, 29/37) and FIV (16.2%, 6/37) indicated a high association between FeLV infection and tumour development in the study region.

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS:

cat; feline immunodeficiency virus; feline leukaemia virus; leukaemia
PMID: 31375152 DOI: 10.1016/j.jcpa.2019.05.002
[Indexed for MEDLINE]
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MeSH terms


Select item 3137515117.
J Comp Pathol. 2019 Jul;170:1-9. doi: 10.1016/j.jcpa.2019.05.001. Epub 2019 Jun 7.
Lipoxygenase-5 Expression in Canine Urinary Bladder: Normal Urothelium, Cystitis and Transitional Cell Carcinoma.
Finotello R1, Schiavo L2, Ressel L3, Frohmader A4, Silvestrini P2, Verin R3.

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Abstract


Transitional cell carcinoma (TCC) is the most common canine urinary tract tumour and mimics human invasive TCC. Human TCCs overexpress lipoxygenase (LOX)-5 and the use of target inhibitors has proven effective in inhibiting neoplastic growth. In this study, we investigated the immunohistochemical expression of LOX-5 in normal canine urinary bladder, cystitis and TCC. The comparative expression of LOX-5, cyclo-oxygenase (COX)-1 and COX-2 among the three tissue groups was also examined. Biopsy samples from cases of cystitis and TCC were reviewed from 2012 to 2016; samples of histologically normal bladder were used as controls. Dogs were excluded if they had received glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs) and/or chemotherapy prior to tissue collection. LOX-5 was expressed in 95% of TCCs, 23% of cases of cystitis and 10% of controls. LOX-5 and COX-2 immunohistochemistry scores were significantly (P <0.01) higher in TCCs versus cystitis and normal bladders. Results of this study support the rationale for further investigation of the use of NSAIDs with dual anti COX-2 and LOX-5 effect for the treatment of canine TCC.

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

KEYWORDS:

cystitis; dog; lipoxygenase; transitional cell carcinoma
PMID: 31375151 DOI: 10.1016/j.jcpa.2019.05.001
[Indexed for MEDLINE]
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Select item 3133543018.
Am J Dermatopathol. 2019 Aug;41(8):e87-e89. doi: 10.1097/DAD.0000000000001392.
An Atypical Fibroxanthoma and Intradermal Nevus Collision Tumor-Potential for Misdiagnosis.
Steel A1, Debbaneh M2, Cassarino D2.

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Abstract


Atypical fibroxanthomas (AFX) are rare cutaneous tumors, which typically present as a solitary ulcerated papule or nodule on sun-damaged skin. Despite malignant-appearing features on histology, AFX typically pursue a benign clinical course. In rare instances, AFX can form collision tumors with other lesions. However, to the best of our knowledge, AFX in collision with a nevus has never been previously reported. In this study, we describe such a lesion for its novelty and challenge in diagnosis, as this case was originally considered to be melanoma arising in a nevus. On histologic examination, there were 2 distinct populations of cells; one composed of markedly atypical and pleomorphic epithelioid and oval to spindled cells, consistent with AFX, and the other, a bland-appearing intradermal nevus with congenital features. The AFX population stained positive with smooth muscle actin, CD10, and CD68 and was negative for S100, SOX10, Melan-A, desmin, pancytokeratin, CK5/6, and p63. Deep to this was a second population of small, bland-appearing melanocytes in a broad, band-like distribution. This unusual collision tumor between AFX and an intradermal nevus highlights the important role immunohistochemistry plays in avoiding the misdiagnosis and potential overtreatment of benign or low-grade lesions, and in identifying potential mimickers.
PMID: 31335430 DOI: 10.1097/DAD.0000000000001392
[Indexed for MEDLINE]
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Select item 3133541619.
Am J Dermatopathol. 2019 Aug;41(8):602-605. doi: 10.1097/DAD.0000000000001348.
Primary Cutaneous Anaplastic Lymphoma Kinase-Positive Large B-Cell Lymphoma.
Kempf W1, Torricelli R2, Zettl A3, Zimmermann AK1, Berisha A1, Ghielmini M4.

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Abstract


Large B-cell lymphomas include several subtypes. Recently, anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma has been delineated as a distinct entity involving mostly lymph nodes and rarely affecting extranodal sites. We describe the first case of a primary cutaneous ALK-positive large B-cell lymphoma in a 48-year-old man with a solitary nodule on the back, and describe the histologic and phenotypic features. Accurate staging confirmed the absence of other lesions, and so surgical excision and postoperative local radiation therapy were initiated and resulted in complete remission. Two years later, extracutaneous spread with involvement of axillary lymph nodes occurred. Complete remission was achieved again by multiagent chemotherapy. Our case demonstrates that a primary cutaneous form of ALK-positive large B-cell lymphoma exists. The immunophenotypic analysis of cutaneous large B-cell lymphomas affecting the skin primarily or secondarily should include the assessment of ALK expression.
PMID: 31335416 DOI: 10.1097/DAD.0000000000001348
[Indexed for MEDLINE]
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Select item 3133541520.
Am J Dermatopathol. 2019 Aug;41(8):596-601. doi: 10.1097/DAD.0000000000001347.
Cutaneous B-Cell Lymphoblastic Lymphoma.
Amarasekera D1, Connolly D2, Gochoco A2, Yang S2, Grosso D3, Flomenberg N3, Shi W4, Alpdogan SO3, Duffy R2, Sahu J2.

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Abstract


B-cell lymphoblastic lymphoma (B-LBL) is a malignant neoplasm of immature B cells that accounts for only 10% of all cases of lymphoblastic lymphoma. Most commonly, B-LBL presents as bony lesions, but in rare cases, the disease manifests cutaneously. We present a case of simultaneous cutaneous and systemic presentation of B-LBL in an otherwise healthy 28-year-old man in which the lymphoblastic infiltrate stained positive for CD79a, Tdt, CD10, and CD20. A diagnosis of cutaneous B-LBL was made, and systemic work-up revealed widespread involvement of the skin, bone, and lymph nodes. Review of all currently described cases of cutaneous B-LBL with or without systemic involvement revealed that the most frequently positive tumor markers were CD79a (92.3%), Tdt (90.6%), and CD10 (83.3%). Systemic involvement of B-LBL was found in nearly half of all cases with cutaneous presentation.
PMID: 31335415 DOI: 10.1097/DAD.0000000000001347
[Indexed for MEDLINE]
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Select item 3133541221.
Am J Dermatopathol. 2019 Aug;41(8):587-589. doi: 10.1097/DAD.0000000000001307.
Cytoimmunofluorescence Diagnosis in Surgically Induced Pemphigus Foliaceus.
Magdaleno-Tapial J, Valenzuela-Oñate C, Giacaman-von der Weth M, García-Legaz Martínez M, Hernández-Bel P, Carballeira-Braña A1, Sánchez-Carazo JL, Alegre-de Miquel V.

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Abstract


Pemphigus foliaceus is an autoimmune bullous disease with autoantibodies against desmoglein 1. Case reports of pemphigus after surgery have also been described, which may simulate an infection of the surgical wound, a contact dermatitis, or even a tumor recurrence. Cytoimmunofluorescence can help to establish a rapid diagnosis.
PMID: 31335412 DOI: 10.1097/DAD.0000000000001307
[Indexed for MEDLINE]
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Select item 3133540722.
Am J Dermatopathol. 2019 Aug;41(8):539-565. doi: 10.1097/DAD.0000000000001287.
PD-L1 Detection-Pearls and Pitfalls Associated With Current Methodologies Focusing on Entities Relevant to Dermatopathology.
Oh KS1, Mahalingam M2,3.

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Abstract


PD-L1 is a transmembrane glycoprotein with an extracellular as well as an intracellular cytoplasmic domain. Physiologically, it plays a pivotal role in regulating T-cell activation and tolerance. Many tumor cells have exploited this regulatory mechanism by overexpressing PD-L1 in an effort to escape immunologic surveillance. In this review, we parse the literature regarding the prognostic value of tumoral PD-L1 expression before discussing the various methodologies as well as the pearls and pitfalls associated with each for predicting response to anti-PD-1/PD-L1 therapies. Special attention is given to cutaneous entities in which PD-L1 expression has been documented with an emphasis on cutaneous malignancies that have seen the broadest applications of anti-PD-L1/PD-1 therapies. Currently, immunohistochemistry is the method that is most commonly used for detection of PD-L1. However, with the wide array of immunohistochemistry protocols and staining platforms available in the market, there seems to be different cutoffs not just for different entities but also for the same entity. This review is an attempt to address the need for standardization and validation of existing protocols for PD-L1 detection.
PMID: 31335407 DOI: 10.1097/DAD.0000000000001287
[Indexed for MEDLINE]
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Select item 3127685323.
World Neurosurg. 2019 Oct;130:e634-e639. doi: 10.1016/j.wneu.2019.06.180. Epub 2019 Jul 2.
Surgical Outcome and Treatment of Thyrotropin-Secreting Pituitary Tumors in a Tertiary Referral Center.
Herguido NG1, Fuentes ED1, Venegas-Moreno E1, Maorad LB1, Flores-Martinez A1, Ruiz PR1, Dueñas MC1, Roldán F2, Fajardo E2, Ruiz-Valdepeñas EC3, Kaen A3, Martín Schrader I3, Cano DA1, Soto-Moreno A4.

Author information


Abstract

OBJECTIVE:

Thyrotropin (TSH)-secreting pituitary tumors are rare and typically present with hyperthyroidism. Here we report the diagnosis, treatment, and surgical outcomes in a series of patients with TSH-secreting pituitary tumors in a tertiary referral center.
METHODS:

Descriptive retrospective study that included all patients with TSH-secreting pituitary tumors who underwent transsphenoidal surgery in the endocrinology and nutrition unit of the Virgen del Rocío University Hospital (Seville, Spain) between 2004 and 2016.
RESULTS:

The mean age at diagnosis was 42.8 ± 17 years. The mean time from onset of symptoms to diagnosis was 13 ± 10 months. Four patients displayed symptoms indicating hyperthyroidism (1 suffered from tachycardia); 3 patients showed symptoms because of mass effect (visual impairment and headache) and 3 patients were diagnosed based on incidental findings after routine blood tests (high free thyroxine levels). Eight patients had macroadenomas, and 2 patients had microadenomas. Five patients underwent conventional pituitary surgery, and 5 patients underwent expanded endoscopic transsphenoidal surgery. Six patients achieved cure after surgery. The other patients received radiotherapy and/or treatment with somatostatin analogs. Analysis of somatostatin receptor (SSTR) expression by immunohistochemistry could be performed in 6 tumors.
CONCLUSIONS:

Our results confirm the clinical and hormonal heterogeneity caused by TSH-secreting pituitary adenomas. Surgery is considered the first choice of treatment for these tumors. We observed surgical cure rates similar to those reported in recent published series. SSTR2 and SSTR3 are highly expressed in TSH-secreting pituitary adenomas. Our results suggest that somatostatin analog treatment may be also helpful in the treatment of TSH-secreting pituitary adenomas.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS:

SSTRs; Somatostatin receptors; TSH-Secreting pituitary tumors
PMID: 31276853 DOI: 10.1016/j.wneu.2019.06.180
[Indexed for MEDLINE]
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Select item 3112015424.
Pediatr Dermatol. 2019 Jul;36(4):477-481. doi: 10.1111/pde.13850. Epub 2019 May 23.
Immunophenotype of pediatric-onset mastocytosis does not correlate with clinical course.
Greenberger S1,2, Landov H1,2, Confino Y2,3, Vaknine H2,4, Avivi C2,5, Baum S1,2, Barzilai A1,2,5.

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Abstract

BACKGROUND:

Pediatric mastocytosis differs from adult mastocytosis in its presentation and clinical course. However, the data regarding the immunophenotypic characterization of mast cells in children are limited. Our objective was to evaluate the immunophenotype of mast cells in pediatric mastocytosis and correlate it with the clinical course.
METHODS:

Biopsy specimens of children with cutaneous mastocytosis were retrieved from the institutions of pathology and were stained for CD25, CD2, and CD30. The percentage of mast cells and the staining intensity were correlated with the clinical data.
RESULTS:

Twenty-five biopsy specimens were included in the study. Patients' average age was 15.4 at presentation and 37.5 months at biopsy performance. Clinical presentations included maculopapular cutaneous mastocytosis in 79% and mastocytoma in 21% of cases. CD25, CD2, and CD30 were positive in 60%, 44%, and 84% of the biopsy specimens, respectively. The staining score was significantly higher for CD30 as compared to those for CD25 and CD2 (P = 0.02). No correlation was found between the immunophenotype and the clinical form or course of disease.
CONCLUSIONS:

Our results confirm that CD30 is a sensitive marker for pediatric-onset mastocytosis. Nevertheless, its expression does not correlate with clinical subtype or clinical course. The sensitivity of CD25 is higher than that of CD2 in skin lesions.

© 2019 Wiley Periodicals, Inc.

KEYWORDS:

CD2; CD25; CD30; mastocytosis; pediatric
PMID: 31120154 DOI: 10.1111/pde.13850
[Indexed for MEDLINE]
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Select item 3101772525.
Diagn Cytopathol. 2019 Oct;47(10):1042-1044. doi: 10.1002/dc.24194. Epub 2019 Apr 24.
Effusion cytology of epithelioid rhabdomyosarcoma.
Renshaw AA1, Gould EW1.

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Abstract


We report a case of epithelioid rhabdomyosarcoma in a pleural effusion. In contrast to most rhabdomyosarcomas in effusions, the cells presented as cohesive clusters of atypical cells with abundant eosinophilic cytoplasm which mimicked an adenocarcinoma. Immunohistochemistry was positive for epithelial membrane antigen and muscle markers and negative for keratins.

© 2019 Wiley Periodicals, Inc.

KEYWORDS:

cytology; effusion; epithelioid rhabdomyosarcoma; rhabdomyosarcoma
PMID: 31017725 DOI: 10.1002/dc.24194
[Indexed for MEDLINE]
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Select item 3100302626.
World Neurosurg. 2019 Aug;128:e195-e208. doi: 10.1016/j.wneu.2019.04.089. Epub 2019 Apr 16.
Dynamic Contrast-Enhanced T1-Weighted Perfusion Magnetic Resonance Imaging Identifies Glioblastoma Immunohistochemical Biomarkers via Tumoral and Peritumoral Approach: A Pilot Study.
Ozturk K1, Soylu E1, Tolunay S2, Narter S2, Hakyemez B3.

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Abstract

OBJECTIVE:

We aimed to evaluate the usefulness of dynamic contrast-enhanced T1-weighted perfusion magnetic resonance imaging (DCE-pMRI) to predict certain immunohistochemical (IHC) biomarkers of glioblastoma (GB) in this pilot study.
METHODS:

We retrospectively reviewed 36 patients (male/female, 25:11; mean age, 53 years; age range, 29-85 years) who had pretreatment DCE-pMRI with IHC analysis of their excised GBs. Regions of interest of the enhancing tumor (ER) and nonenhancing peritumoral region (NER) were used to calculate DCE-pMRI parameters of volume transfer constant, back flux constant, volume of the extravascular extracellular space, initial area under enhancement curve, and maximum slope. IHC biomarkers including Ki-67 labeling index, epidermal growth factor receptor (EGFR), oligodendrocyte transcription factor 2 (OLIG2), isocitrate dehydrogenase 1 (IDH1), and p53 mutation status were determined. The imaging metrics of GB with IHC markers were compared using the Kruskal-Wallis test and Spearman correlation analysis.
RESULTS:

Among 30 patients with available IDH1 status, 14 patients (46.6%) had IDH1 mutation. EGFR amplification was present in 24/36 (66.6%) patients. Mean Ki-67 labeling index was 29% (range, 1.5%-80%). p53 mutation was present in 20/36 GBs (55%), whereas OLIG2 expression was positive in 29/36 GBs (80.5%). Various DCE-pMRI parameters gathered from the ER and NER were significantly correlated with IDH1 mutation, EGFR amplification, and OLIG2 expression (P < 0.05). Ki-67 labeling index showed a strong positive correlation with initial area under enhancement curve (r = 0.619; P < 0.001).
CONCLUSIONS:

DCE-pMRI could determine surrogate IHC biomarkers in GB via tumoral and peritumoral approach, potential targets for individualized treatment protocols.

Copyright © 2019. Published by Elsevier Inc.

KEYWORDS:

Dynamic contrast-enhanced T1-weighted perfusion MR imaging (DCE-pMRI); Epidermal growth factor receptor (EGFR); Glioblastoma (GB); Isocitrate dehydrogenase 1 (IDH1); Oligodendrocyte transcription factor 2 (OLIG2)
PMID: 31003026 DOI: 10.1016/j.wneu.2019.04.089
[Indexed for MEDLINE]
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Select item 3095891427.
Prostate. 2019 Jun;79(9):949-960. doi: 10.1002/pros.23802. Epub 2019 Apr 8.
Optimizing live-animal bioluminescence imaging prediction of tumor burden in human prostate cancer xenograft models in SCID-NSG mice.
Kim S1, Zhang Y2, Tang S2, Qin C1,3, Karelia D1, Sharma A1,4, Jiang C1, Lu J1,4.

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Abstract

BACKGROUND:

Noninvasive live-animal longitudinal monitoring of xenograft tumor growth and metastasis by bioluminescent imaging (BLI) has been widely reported in cancer biology and preclinical therapy literature, mainly in athymic nude mice. Our own experience at calibrating BLI readout with tumor weight/volume in human prostate cancer xenograft models in haired, SCID-NSG mice through intraprostatic (orthotopic) and subcutaneous (SC) inoculations revealed either nonexistent or poor correlation (coefficient of determination, R 2  = ~0.01-0.3). The present work examined several technical and biological factors to improve BLI utility.
METHODS:

After ruling out promoter-luciferase (luc) specificity and luc gene loss in the cell inoculum with LNCaP-AR-luc cells expressing an androgen receptor (AR) and tagged with AR-responsive probasin promoter-luc gene, we evaluated different routes of d-luciferin administration, imaging time during the day, charge-coupled device camera image acquisition settings, and hair removal methods to improve the imaging protocol. For most imaging sessions, BLI was carried out within the same day of tumor volume measurement. After necropsy, histological and immunohistochemical (IHC) analyses were performed on the tumors to evaluate necrosis and expression of luciferase and AR, respectively.
RESULTS:

Injection of d-luciferin by SC route, robust image-capture setting (30 000 counts and autoexposure), imaging in the morning and thorough hair removal resulted in a substantial improvement of R2 to ~0.6. Histological analyses confirmed the lack of BLI signal in necrotic tumor masses consistent with luciferase-mediated light emission only in oxygenated adenosine triphosphate-producing viable cells. IHC staining detected heterogeneous expression of luciferase tracking generally with AR expression in nonnecrotic tumor tissues.
CONCLUSIONS:

Our body of work highlighted a framework to validate imaging protocols to ensure the acquisition of interpretable BLI data as an indicator of xenograft tumor burden. The vast tissue heterogeneity in prostate tumor xenografts and variable luciferase expression constrained this technology from achieving a high correlation.

© 2019 Wiley Periodicals, Inc.

KEYWORDS:

IVIS instrumental setting; bioluminescence; heterogeneous expression of luciferase; necrosis; prostate cancer
PMID: 30958914 PMCID: PMC6668996 [Available on 2020-06-01] DOI: 10.1002/pros.23802
[Indexed for MEDLINE]
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Select item 3094178728.
Pediatr Dermatol. 2019 Jul;36(4):509-510. doi: 10.1111/pde.13824. Epub 2019 Apr 2.
Disseminated De Novo Myeloid Sarcoma in a 17-year-old Boy.
Sandre MK1, Liu A1, Levy R2.

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Abstract


Myeloid sarcoma (MS) is a rare extramedullary tumor of malignant myeloid cells often associated with acute myeloid leukemia. We report a case of a 17-year-old boy presenting with diffuse red-brown skin nodules ultimately diagnosed with the scarcely described disseminated, de novo MS. It is important for dermatologists to keep MS on their differential when assessing patients with disseminated red-brown nodules.

© 2019 Wiley Periodicals, Inc.

KEYWORDS:

acute myeloid leukemia; chloroma; granulocytic sarcoma; myeloid sarcoma
PMID: 30941787 DOI: 10.1111/pde.13824
[Indexed for MEDLINE]
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Select item 3089564029.
Histopathology. 2019 Aug;75(2):174-184. doi: 10.1111/his.13865. Epub 2019 Mar 21.
Low-grade oncocytic tumour of kidney (CD117-negative, cytokeratin 7-positive): a distinct entity?
Trpkov K1, Williamson SR2, Gao Y1, Martinek P3, Cheng L4, Sangoi AR5, Yilmaz A1, Wang C6, San Miguel Fraile P7, Perez Montiel DM8, Bulimbasić S9, Rogala J10, Hes O3.

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Abstract

AIM:

To describe a group of distinct low-grade oncocytic renal tumours that demonstrate CD117 negative/cytokeratin (CK) 7-positive immunoprofile.
METHODS AND RESULTS:

We identified 28 such tumours from four large renal tumour archives. We performed immunohistochemistry for: CK7, CD117, PAX8, CD10, AMACR, e-cadherin, CK20, CA9, AE1/AE3, vimentin, BerEP4, MOC31, CK5/6, p63, HMB45, melan A, CD15 and FH. In 14 cases we performed array CGH, with a successful result in nine cases. Median patient age was 66 years (range 49-78 years) with a male-to-female ratio of 1:1.8. Median tumour size was 3 cm (range 1.1-13.5 cm). All were single tumours, solid and tan-brown, without a syndromic association. On microscopy, all cases showed solid and compact nested growth. There were frequent areas of oedematous stroma with loosely arranged cells. The tumour cells had oncocytic cytoplasm with uniformly round to oval nuclei, but without significant irregularities, and showed only focal perinuclear halos. Negative CD117 and positive CK7 reactivity were present in all cases (in two cases there was focal and very weak CD117 reactivity). Uniform reactivity was found for PAX8, AE1/AE3, e-cadherin, BerEP4 and MOC31. Negative stains included CA9, CK20, vimentin, CK5/6, p63, HMB45, Melan A and CD15. CD10 and AMACR were either negative or focally positive; FH was retained. On array CGH, there were frequent deletions at 19p13.3 (seven of nine), 1p36.33 (five of nine) and 19q13.11 (four of nine); disomic status was found in two of nine cases. On follow-up (mean 31.8 months, range 1-118), all patients were alive with no disease progression.
CONCLUSION:

Low-grade oncocytic tumours that are CD117-negative/CK7-positive demonstrate consistent and readily recognisable morphology, immunoprofile and indolent behaviour.

© 2019 John Wiley & Sons Ltd.

KEYWORDS:

chromophobe renal cell carcinoma; hybrid oncocytic tumour; hybrid tumour; low-grade oncocytic tumour; oncocytoma; unclassified oncocytic tumour; unclassified renal carcinoma
PMID: 30895640 DOI: 10.1111/his.13865
[Indexed for MEDLINE]
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Select item 3089319030.
Ophthalmic Plast Reconstr Surg. 2019 Sep/Oct;35(5):495-502. doi: 10.1097/IOP.0000000000001355.
Small Benign Storiform Fibrous Tumor (Fibrous Histiocytoma) of the Conjunctival Substantia Propria in a Child: Review and Clarification of Biologic Behavior.
Tieger MG1, Jakobiec FA, Ma L, Wolkow N.

Author information


Abstract

PURPOSE:

A case of a small benign storiform fibrous tumor of the conjunctival substantia propria is described to clarify the category of fibrous histiocytoma. In addition, a comparison of the various spindle cell tumors of the conjunctival substantia propria is explored.
METHODS:

The patient underwent a complete tumor excision, and the specimen was analyzed by histopathologic and immunohistochemical investigations.
RESULTS:

A cellular mass, composed solely of spindle cells in a storiform pattern without a component of histiocytic cells, was found beneath an undisturbed nonkeratinizing squamous epithelium and was separated from the epithelium by a grenz zone of uninvolved collagen. The lesion was sharply demarcated but not encapsulated. The Masson trichrome stain revealed scant deposition of intercellular collagen. The reticulin stain displayed numerous and delicate wiry fibers between the tumor cells and encircling capillaries. The Alcian blue stain demonstrated faint positivity in the interstitium. Immunohistochemistry revealed positivity for vimentin, factor XIIIa, smooth muscle actin, CD10, and CD45. Negative stains were obtained for CD34, CD56, S100, desmin, and Ki67.
CONCLUSIONS:

The broad term of fibrous histiocytoma should be reserved for deep fibroblastic spindle cell tumors (e.g., those of the orbit) that display an aggressive behavior. More benign superficial spindle cell tumors of the dermis are now preferentially characterized as dermatofibromas. It is suggested that equally benign epibulbar tumors should no longer be designated as fibrous histiocytomas but rather as benign storiform fibrous tumors. Tumors completely composed of polygonal histiocytoid (epithelioid) cells that are CD34+ should be excluded from the benign storiform fibrous tumor category. Positive smooth muscle actin and factor XIIIa staining in conjunction with negative staining for CD34 and desmin in the current spindled tumor cells are findings consistent with those of cutaneous dermatofibromas. Both the epibulbar and dermal spindle cell lesions have displayed an indolent and nonaggressive behavior. Microscopically they contain a high proportion of dendrocytic stellate cells that are either factor XIIIa+ or XIIIa-. Given the anatomic differences between the dermis and conjunctiva, the term dermatofibroma is inappropriate for the current tumor; instead the term benign storiform fibrous tumor has been proposed for superficial tumors of the conjunctiva.
PMID: 30893190 DOI: 10.1097/IOP.0000000000001355
[Indexed for MEDLINE]
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Select item 3088292231.
Histopathology. 2019 Aug;75(2):202-212. doi: 10.1111/his.13862. Epub 2019 Jun 17.
Elevated HSP90 associates with expression of HIF-1α and p-AKT and is predictive of poor prognosis in nasopharyngeal carcinoma.
Feng J1, Xie G2, Zhan Y1, Lu J1, Xu L1, Fan S1, Wang W1.

Author information


Abstract

AIMS:

HSP90, as a molecular chaperone, has numerous substrate proteins, including HIF-1α and p-AKT, but the relationships among HSP90, HIF-1α and p-AKT have not been investigated in NPC. We examined and analysed the correlation between expression of HSP90, HIF-1α and p-AKT and clinicopathological features of NPC.
METHODS:

We collected 445 cases of NPC and 54 cases of non-cancerous nasopharyngeal epithelia tissues, detected expression of HSP90, HIF-1α and p-AKT proteins in these tissues by immunohistochemistry.
RESULTS:

The results indicated that overexpression of HSP90, HIF-1α and p-AKT in NPC was significantly higher than that in non-cancerous nasopharyngeal epithelia (P < 0.05). The overexpression of HIF-1α in primary NPC was significantly lower than that in matched lymph node metastatic NPC (P = 0.024) or recurrent NPC (P = 0.039). The overexpression of HSP90 (P < 0.001) and HIF-1α (P = 0.031) was evidently higher in late stage NPC. NPC patients with lymph node metastasis (LNM) had a higher overexpression rate of HSP90 (P < 0.001) than those without LNM. Increased HSP90 expression was positively associated with HIF-1α expression (r = 0.367, P < 0.001) and p-AKT (r = 0.142, P = 0.003) expression in NPC. Furthermore, HIF-1α was also related to p-AKT expression (r = 0.114, P = 0.017). The overall survival rate for NPC patients with up-regulated HSP90 was significantly lower than those with down-regulated HSP90 (P < 0.001), as was found with raised HIF-1α (P = 0.036) and increased p-AKT (P = 0.044). Multivariate Cox regression analysis further identified that HSP90 and HIF-1α were independent poor prognostic factors for NPC.
CONCLUSIONS:

Taken together, elevated HSP90 was associated with expression of HIF-1α and p-AKT in NPC. Furthermore, high expression of HSP90 and HIF-1α could be used as a novel independent poor prognostic biomarker for patients with NPC.

© 2019 John Wiley & Sons Ltd.

KEYWORDS:

HIF-1α; HSP90; nasopharyngeal carcinoma; p-AKT; prognosis
PMID: 30882922 DOI: 10.1111/his.13862
[Indexed for MEDLINE]
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Select item 3086507032.
Ophthalmic Plast Reconstr Surg. 2019 Sep/Oct;35(5):478-483. doi: 10.1097/IOP.0000000000001333.
Orbital Nasal-Type Extranodal Natural Killer/T-Cell Lymphoma: An Ongoing Diagnostic Challenge Further Confounded by Small-Cell Predominance.
Wolkow N1,2, Jakobiec FA2, Habib LA1, Freitag SK1.

Author information


Abstract

PURPOSE:

To highlight the histopathologic diagnostic challenges of small-cell predominant extranodal nasal-type natural killer/T-cell lymphoma (ENTNKT) of the orbit.
METHODS:

Retrospective chart review and histopathologic study with immunohistochemistry and in situ hybridization of 3 cases.
RESULTS:

Three cases of ENTNKT presented to the Mass Eye and Ear emergency room as orbital cellulitis over 1 year. The first case was unusual in that there was a predominance of small cells, giving the ENTNKT the histopathologic appearance of a nonmalignant inflammatory process. This challenging case is juxtaposed alongside 2 other cases, which exhibited the more typical lymphomatous microscopic appearance.
DISCUSSION:

ENTNKT can extend into the orbit from the adjacent sinuses or rarely arise primarily in the orbit. A diagnosis is typically made with a biopsy. Occasionally, however, the histopathologic diagnosis can be elusive when a predominance of small lymphomatous cells that are virtually indistinguishable from non-neoplastic inflammatory cells is present. Demonstration of CD56 positivity by immunostaining and in situ hybridization for Epstein-Barr virus are essential in confirming the diagnosis.
CONCLUSIONS:

ENTNKT should be considered both in the clinical and histopathologic differential diagnoses of orbital infections and idiopathic inflammations (pseudotumor).
PMID: 30865070 DOI: 10.1097/IOP.0000000000001333
[Indexed for MEDLINE]
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Select item 3086257433.
World Neurosurg. 2019 Jun;126:570-575. doi: 10.1016/j.wneu.2019.02.163. Epub 2019 Mar 9.
Case of Acromegaly Caused by Rathke Cleft Cyst Mimicking Plurihormonal Pituitary Adenoma.
Morinaga Y1, Nii K2, Sakamoto K2, Inoue R2, Mitsutake T2, Hanada H2.

Author information


Abstract

BACKGROUND:

Acromegaly caused by Rathke cleft cyst (RCC) mimicking a plurihormonal pituitary adenoma (PA) is rare.
CASE DESCRIPTION:

We report a 71-year-old woman who presented with hyperhidrosis in 2013. Magnetic resonance imaging performed in April 2018 revealed that the patient had a pituitary tumor, and she was referred to our hospital. She presented with an acromegaly-like appearance with mild hypertrophy at her limb extremities. Preoperative blood tests, magnetic resonance imaging, and an endocrine tolerance test indicated that the patient's symptoms satisfied the diagnostic criteria for acromegaly, with a suspected diagnosis of an RCC and growth hormone (GH)-producing PA. Endoscopic transsphenoidal surgery (eTSS) was performed. Permanent pathologic diagnosis showed an RCC mimicking a plurihormonal PA, which was confirmed via immunohistochemistry. Blood sampling 2 months post surgery showed reduced GH (0.41 ng/mL) and increased insulin-like growth factor-1 (IGF-1) (356 ng/mL) levels. In addition, a postoperative endocrine tolerance test revealed a parasitic reaction of GH and secondary adrenocortical hypofunction. No RCC recurrence was found, and the GH (0.32 ng/mL) and previously increased IGF-1 (169 ng/mL) levels were normalized 12 months after eTSS.
CONCLUSIONS:

We reported a rare case of acromegaly caused by RCC mimicking a plurihormonal PA. This case suggests that inflammation associated with RCC might be involved in the development of adenomatous cells. Postoperative clinical symptoms and elevated fibrinogen and IGF-1 levels later improved. This outcome suggested that the transient increase in IGF-1 2 months after surgery might reflect RCC-induced inflammation.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS:

Acromegaly; GH; Plurihormonal pituitary adenoma; Rathke cleft cyst
PMID: 30862574 DOI: 10.1016/j.wneu.2019.02.163
[Indexed for MEDLINE]
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Select item 3085964834.
Pediatr Dermatol. 2019 Jul;36(4):490-496. doi: 10.1111/pde.13805. Epub 2019 Mar 11.
Plexiform fibrohistiocytic tumor on the chest of a 5-year-old child and review of the literature.
Valiga A1, Neidig L1, Cusack CA1, Gaddis K2,3, Jen M2,3, Rubin A2,3, Moon AT1,2,3.

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Abstract


Plexiform fibrohistiocytic tumor (PFT) is a rare neoplasm of mesenchymal origin that can be identified by its propensity for children and adolescents combined with a characteristic histologic arrangement of histiocytes and osteoclast-like giant cells whorled within tumor islands. A 5-year-old female presented with a raised, intermittently tender, and slowly enlarging tumor on her chest, which was histologically confirmed to be a PFT. We present this case along with a comprehensive review of PFT cases reported in the literature to describe the demographic, histologic, and rarely metastatic behavior of this entity. It is important to include PFT on the differential diagnosis of an enlarging tumor in the pediatric population.

© 2019 Wiley Periodicals, Inc.

KEYWORDS:

dermatopathology; lumps/bumps; neoplasms-benign
PMID: 30859648 DOI: 10.1111/pde.13805
[Indexed for MEDLINE]
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Select item 3074584935.
Int J Biol Sci. 2019 Jan 1;15(3):628-635. doi: 10.7150/ijbs.30652. eCollection 2019.
The KLF14 Transcription Factor Regulates Glycolysis by Downregulating LDHB in Colorectal Cancer.
Wu G1, Yuan S1, Chen Z1, Chen G1, Fan Q1, Dong H1, Ye F1, Li J2, Zhu X1.

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Abstract


The Krüppel-like transcription factor 14 (KLF14) is a critical regulator of a wide array of biological processes. However, the role of KLF14 in colorectal cancer (CRC) isn't fully investigated. This study aimed to explore the clinicopathological significance and potential role of KLF14 in the carcinogenesis and progression of CRC. A tissue microarray consisting of 185 samples from stage I-III CRC patients was adopted to analyze the correlation between KLF14 expression and clinicopathological parameters, as well as overall survival (OS) and disease-free survival (DFS). The underlying mechanisms of altered KLF14 expression on glycolysis were studied using in vitro and patients' samples. The results showed that KLF14 expression was downregulated in CRC than their normal controls. Low KLF14 expression correlated with advanced T stage (P< 0.001) and N stage (P= 0.040), and larger tumor size (P= 0.008). Lost KLF14 expression implied shorter OS and DFS after colectomy in both univariate and multivariate survival analysis (P<0.05). Experimentally, restore KLF14 expression significantly decreased the rate of glycolysis both in vitro and in patients' sample. Mechanically, KLF14 regulated glycolysis by downregulating glycolytic enzyme LDHB. Collectively, KLF14 is a novel prognostic biomarker for survival in CRC, and downregulation of KLF14 in CRC prompts glycolysis by target LDHB. Hence, KLF14 could constitute potential prognostic predictors and therapeutic targets for CRC.

KEYWORDS:

Colorectal Cancer; Glycolysis; KLF14; LDHB
PMID: 30745849 PMCID: PMC6367579 DOI: 10.7150/ijbs.30652
[Indexed for MEDLINE] Free PMC Article
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Select item 3074584036.
Int J Biol Sci. 2019 Jan 1;15(3):533-543. doi: 10.7150/ijbs.30114. eCollection 2019.
RRM2 is a potential prognostic biomarker with functional significance in glioma.
Sun H1, Yang B1,2, Zhang H1, Song J1, Zhang Y1, Xing J3, Yang Z3, Wei C4, Xu T5, Yu Z5, Xu Z1,2, Hou M1, Ji M1,2, Zhang Y5.

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Abstract


Glioma is one of the most common brain tumors, suggesting the importance of investigating the molecular mechanism of gliomas. We studied the roles of Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in glioma. Expressions of RRM2 are higher in glioma tissues evidenced by TCGA data, western blot and immunohistochemistry. RRM2 is negatively correlated with glioma patient's survival. RNA-seq showed that genes involved in apoptosis, proliferation, cell adhesion and negative regulation of signaling were up-regulated upon RNAi-mediated knock-down of RRM2. Cell phenotypes specific for stably knocking down RRM2 were determined using stable transfection in vitro. In an in vivo model, knock-down of RRM2 inhibited tumor growth and caused suppression of AKT and ERK1/2 signalings. Interfering RRM2 also down-regulated the expression of cyclin A, cyclin B1, cyclin D1, Vimentin, and N-cadherin, and elevated E-cadherin expression. Moreover, overexpression of RRM2 failed to increase the expression of cyclin B1, cyclin D1, and N-cadherin when phosphorylation of AKT and ERK1/2 was suppressed by LY294002 or PD98059. These findings indicated that RRM2 is a positive regulator of glioma progression which contributes to the migration and proliferation of glioma cells through ERK1/2 and AKT signalings and might be a novel prognostic indicator for glioma patients.

KEYWORDS:

AKT; ERK1/2; G2/M phase arrest; Knock-down; RRM2
PMID: 30745840 PMCID: PMC6367584 DOI: 10.7150/ijbs.30114
[Indexed for MEDLINE] Free PMC Article
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Select item 3074583937.
Int J Biol Sci. 2019 Jan 1;15(3):522-532. doi: 10.7150/ijbs.30572. eCollection 2019.
Combined Androgen receptor blockade overcomes the resistance of breast cancer cells to palbociclib.
Ji W1, Shi Y2, Wang X2, He W1, Tang L2, Tian S3, Jiang H4, Shu Y5, Guan X1,2,5.

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Abstract


The dysregulation of cyclin D -Cyclin-dependent kinase 4/6 (CDK4/6)-Rb axis has been implicated in breast cancer progression and the selective CDK4/6 inhibitors have shown effective activity in advanced breast cancer, especially in tumors driven by the estrogen receptor (ER). However, resistance to these small molecular inhibitors has become an inevitable clinical issue after their initial use. Here, we investigated the potential mechanism of resistance by establishing a CDK4/6 inhibitor palbociclib-resistant breast cancer cell line (MCF-7pR). After prolonged exposure to palbociclib, we detected the loss of the ER signaling and an increase in androgen receptor (AR). Moreover, we demonstrated more localization of AR in the cell nucleus of MCF-7pR compared to the parental cell (MCF-7). We also reported that AR could promote the progression of the cell cycle. Blockade of AR signaling could reduce the level of the relative G1-S cyclins, abolish Rb phosphorylation and inhibit the activation of transcriptional programs in S phase. Furthermore, dual inhibition of AR and CDK4/6 could reverse the resistance of palbociclib both in vitro and in vivo. In sum, our studies provide evidence that AR activation promotes cell cycle progression and cell proliferation in CDK4/6 inhibitor resistance, and identify AR inhibition as a putative novel therapeutic strategy to treat CDK4/6 inhibitor resistance in cancer.

KEYWORDS:

breast cancer; cell cycle; drug resistance; enzalutamide; palbociclib
PMID: 30745839 PMCID: PMC6367574 DOI: 10.7150/ijbs.30572
[Indexed for MEDLINE] Free PMC Article
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Select item 3071568338.
Biol Trace Elem Res. 2019 Oct;191(2):443-452. doi: 10.1007/s12011-019-1641-x. Epub 2019 Feb 4.
Glutathione Might Attenuate Cadmium-Induced Liver Oxidative Stress and Hepatic Stellate Cell Activation.
Ren L1, Qi K2, Zhang L1,3, Bai Z1,2, Ren C1, Xu X1, Zhang Z1, Li X4,5,6.

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Abstract


The liver is a major organ involved in cadmium (Cd)-induced oxidative damage. Following liver injury, hepatic stellate cells (HSCs) are activated to participate in the wound healing process, but also facilitate liver fibrosis. Previous studies have observed fibrogenic effects of Cd on liver. However, the oxidative stress mechanisms of Cd-induced HSC activation as well as whether administration of glutathione (GSH) alleviates this activation, remain unclear. In this study, 24 rats were divided randomly into four experimental groups: control, GSH-treated, Cd-treated, and Cd + GSH-treated. After 4 weeks, the liver injury index, HSC-specific activation markers, oxidative stress-related antioxidants, and enzyme activities and signals were measured. Cd uptake and the generation of reactive oxygen species (ROS) in hepatocytes were detected by mass cytometry and fluorescence microscopy, respectively. Levels of aspartate aminotransferase, xanthine oxidase, γ-glutamyl transpeptidase, and α-smooth muscle actin (αSMA) were significantly increased in Cd-treated rats. Activated HSCs positive for αSMA expression and excess collagen deposition were detected in the Cd-treated group. In contrast, activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase were reduced. Supplementation with GSH reversed some of the Cd-induced effects and increased the protein level of phosphorylated (p)-P65 while decreasing p-JNK. Pretreatment with GSH lowered Cd uptake and ROS generation in hepatocytes in vitro. These results indicate that administration of GSH was effective in attenuating Cd-induced oxidative stress via decreasing Cd uptake, restoring the activities of oxidative enzymes, activating NF-κB, inhibiting the JNK signaling pathway, and preventing excessive ROS generation and HSC activation.

KEYWORDS:

Cadmium; Glutathione; Hepatic stellate cell activation; Oxidative stress
PMID: 30715683 DOI: 10.1007/s12011-019-1641-x
[Indexed for MEDLINE]
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Select item 3064392939.
Cancer Chemother Pharmacol. 2019 Apr;83(4):639-647. doi: 10.1007/s00280-019-03769-7. Epub 2019 Jan 14.
Analysis of SPARC and TUBB3 as predictors for prognosis in esophageal squamous cell carcinoma receiving nab-paclitaxel plus cisplatin neoadjuvant chemotherapy: a prospective study.
Gong L1, Mao W2,3, Chen Q3, Jiang Y2,3, Fan Y4,5.

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Abstract

PURPOSE:

The purpose of the study is to evaluate the predictive efficacy of secreted protein, acidic and rich in cysteine (SPARC) and the class III β-tubulin (β-tubulin III, TUBB3) in predicting therapeutic effect in patients with locally advanced esophageal squamous cell carcinoma(ESCC) who received nab-paclitaxel plus cisplatin neoadjuvant chemotherapy(CT) followed by surgery.
METHODS:

Patients with stage II to III esophageal squamous cell carcinoma of different stages are recruited. The tumor biopsy tissues prior treatment from enrolled patients were examined by SPARC and TUBB3 immunohistochemistry (IHC). Correlations between SPARC/TUBB3 expression and response to chemotherapy and long-term survival in patients received surgical resection was analyzed.
RESULTS:

A total of 35 patients with stage II to III esophageal squamous cell carcinoma were enrolled. Of the 35 enrolled patients, 30 successfully completed neoadjuvant chemotherapy and underwent R0 resection, 3 refused surgery after chemotherapy, and 2 failed to undergo radical surgery after chemotherapy. Out of patients undergoing surgery, pathological complete response (pCR) was achieved in 6 patients (6/30, 20%). The 1, 2 and 5-year disease free survival (DFS) rates were 70.0%, 36.6% and 33.3%, respectively. The 1, 2 and 5-year overall survival (OS) rates were 83.3%, 63.3% and 36.6%, respectively. SPARC and TUBB3 IHC was performed on the tumor biopsy tissues which were obtained from patients before treatment. Correlation between SPARC/TUBB3 expression and long-term survival in patients was studied. Both the median DFS and OS between SPARC negative samples and SPARC positive staining samples have no statistical difference. However, the median DFS and OS in TUBB3 negative patients was better than those in TUBB3 positive patients (p = 0.002 for DFS, p = 0.001 for OS). In addition, patients with pCR had longer OS and DFS time than those without pCR.COX regression analysis showed that TUBB3 prior treatment and pCR were independent prognostic factors in ESCC patients undergoing sequential surgery after preoperative chemotherapy.
CONCLUSIONS:

TUBB3 negative expression prior treatment and pCR may indicate a better prognosis for stage II and III ESCC patients after nab-paclitaxel plus cisplatin neoadjuvant chemotherapy following radical esophagectomy.

KEYWORDS:

Class III β-tubulin; Esophageal carcinoma; Nab-paclitaxel; Neoadjuvant chemotherapy; Secreted protein acidic and rich in cysteine
PMID: 30643929 DOI: 10.1007/s00280-019-03769-7
[Indexed for MEDLINE]
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Select item 3063559040.
Sci Rep. 2019 Jan 11;9(1):75. doi: 10.1038/s41598-018-36171-z.
Role of ultrasonographic features and quantified BRAFV600E mutation in lymph node metastasis in Chinese patients with papillary thyroid carcinoma.
Guo L1, Ma YQ2, Yao Y3, Wu M4, Deng ZH5, Zhu FW2, Luo YK4, Tang J6.

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Abstract


The association between cervical lymph node metastasis (LNM) and ultrasonographic features as well as BRAFV600E mutations in patients with papillary thyroid carcinoma (PTC) remained controversial. This study investigated the association between LNM and ultrasonographic features as well as BRAFV600E mutation in Chinese patients with PTC. A total of 280 patients with PTC in China were included in this study. 108 had cervical lymph node metastasis, while 172 had not. Younger age (<45years) and several ultrasonographic features were significantly associated with cervical LNM (Ps < 0.05). The BRAFV600E mutation was detected in 81.0% of patients with PTC (226/280). The status of BRAFV600E mutation was not associated with cervical LNM. However, Ct values by PCR and intensity of reactions by immunohistochemistry (IHC) for BRAFV600E expression had shown significant difference between group with and without LNM. Furthermore, an increased proportion of LNM was also found with the incremental intensity of IHC for BRAFV600E expression from weak to strong reaction after adjusted potential confounders. Further studies are required to verify this association and explore the intrinsic mechanism.
PMID: 30635590 PMCID: PMC6329760 DOI: 10.1038/s41598-018-36171-z
[Indexed for MEDLINE] Free PMC Article
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Select item 2973141941.
Acad Radiol. 2019 Feb;26(2):247-256. doi: 10.1016/j.acra.2018.04.010. Epub 2018 May 3.
Is There a Direct Correlation Between Microvascular Wall Structure and k-Trans Values Obtained From Perfusion CT Measurements in Lymphomas?
Horger M1, Fallier-Becker P2, Thaiss WM1, Sauter A3, Bösmüller H2, Martella M2, Preibsch H1, Fritz J4, Nikolaou K1, Kloth C5.

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Abstract

RATIONALE AND OBJECTIVES:

This study aimed to test the hypothesis that ultrastructural wall abnormalities of lymphoma vessels correlate with perfusion computed tomography (PCT) kinetics.
MATERIALS AND METHODS:

Our local institutional review board approved this prospective study. Between February 2013 and June 2016, we included 23 consecutive subjects with newly diagnosed lymphoma, who were referred for computed tomography-guided biopsy (6 women, 17 men; mean age, 60.61 ± 12.43 years; range, 28-74 years) and additionally agreed to undergo PCT of the target lymphoma tissues. PCT was obtained for 40 seconds using 80 kV, 120 mAs, 64 × 0.6-mm collimation, 6.9-cm z-axis coverage, and 26 volume measurements. Mean and maximum k-trans (mL/100 mL/min), blood flow (BF; mL/100 mL/min) and blood volume (BV) were quantified using the deconvolution and the maximum slope + Patlak calculation models. Immunohistochemical staining was performed for microvessel density quantification (vessels/m2), and electron microscopy was used to determine the presence or absence of tight junctions, endothelial fenestration, basement membrane, and pericytes, and to measure extracellular matrix thickness.
RESULTS:

Extracellular matrix thickness as well as the presence or absence of tight junctions, basal lamina, and pericytes did not correlate with computed tomography perfusion parameters. Endothelial fenestrations correlated significantly with mean BFdeconvolution (P = .047, r = 0.418) and additionally was significantly associated with higher mean BVdeconvolution (P < .005). Mean k-transPatlak correlated strongly with mean k-transdeconvolution (r = 0.939, P = .001), and both correlated with mean BFdeconvolution (P = .001, r = 0.748), max BFdeconvolution (P = .028, r = 0.564), mean BVdeconvolution (P = .001, r = 0.752), and max BVdeconvolution (P = .001, r = 0.771). Microvessel density correlated with max k-transdeconvolution (r = 0.564, P = .023). Vascular endothelial growth factor receptor-3 expression (receptor specific for lymphatics) correlated significantly with max k-transPatlak (P = .041, r = 0.686) and mean BFdeconvolution (P = .038, r = 0.695).
CONCLUSION:

k-Trans values of PCT do not correlate with ultrastructural microvessel features, whereas endothelial fenestrations correlate with increased intra-tumoral BVs.

Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

Immunohistochemical staining; Perfusion CT; endothelial fenestrations; lymphoma; ultrastructural microvessel features
PMID: 29731419 DOI: 10.1016/j.acra.2018.04.010
[Indexed for MEDLINE]
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