Does LC3 have a role in colorectal carcinoma of Egyptian patients? Rehab M Samaka, Shereen N El Mashad, Nanis S Holah, Rania M Makboul, Shimaa S Elkholy Egyptian Journal of Pathology 2019 16(1):1-10 Background and aim In Egypt, colorectal cancer (CRC) constitutes 4.2% and comes at rank seventh in men and fourth in women. Autophagy is considered an intracellular homeostatic pathway that is related to cancer and other diseases. The role of autophagy with CRC carcinogenesis and tumor progression is uncertain. LC3 is a specific marker for autophagy. The aim of this study is to evaluate the role of autophagy markers LC3A and LC3B in CRC. Materials and methods This retrospective case–control study included 158 colorectal specimens including 87 chemo-naive CRC cases, 12 adenomas, and 59 nonneoplastic colonic tissue cases from Egyptian patients; all cases were stained for LC3A and LC3B antibodies. Results LC3A showed significant epithelial and stromal expression in nonneoplastic colon cases (P=0.02 and 0.015, respectively). There were significant associations between LC3A epithelial overexpression and low-grade CRC cases and long survival (P=0.01 and 0.016, respectively). There was no significant association between LC3B epithelial and stroma expression with histopathological parameters or between three groups. Conclusion The low expression of LC3A could be incriminated in the pathogenesis of CRC and short-term overall survival in Egyptian patients. However, LC3B might be considered as a surrogate marker in our study.

Immunohistochemical expression of forkhead box M1 in colorectal carcinoma Ahmed A Soliman, Lubna O Abdel-Salam, Mohamed A Hussein, Amany M Abdelaziz Egyptian Journal of Pathology 2019 16(1):11-17 Aim There is an urgent need to identify the markers of colorectal cancer (CRC) progression and invasiveness to be more accurate in predicting prognosis. Forkhead box (Fox) family proteins are involved in cell growth and differentiation. FoxM1 is a cell cycle-regulated protein; its deregulation has been implicated in the pathogenesis of many cancers because of its ability to drive cell cycle progression and evasion of growth arrest. We studied the immunohistochemical expression of FoxM1 in CRC in correlation with different clinicopathological aspects. Materials and methods We investigated the immunohistochemical expression of FoxM1 using the appropriate antibody in 32 cases of CRC of which 27 cases were of grade II and five cases were of grade III. Results High expression is detected in 81.3% of cases and low expression in 18.7% of cases. FoxM1 high expression was seen in 58.3% free of nodal metastasis (N0) and in 95% of cases positive for nodal metastasis (N1 and N2). FoxM1 high expression was detected in 54.6% of stage I/II and in 95.2% of stage III/IV. High FoxM1 expression was detected in 94.4% of cases on the left side and rectum and in 64.3% of cases on the right side involving the transverse colon. This means that FoxM1 expression is correlated with the status of nodal metastasis (N), the stage of tumor, and the site of tumor whether right or left. Conclusion FoxM1 high expression was in correlation with increasing stage in CRC, positive nodal metastasis, and site of tumor whether right or left side. There was lack of correlation between FoxM1 expression and some clinicopathological aspects such as age, sex, size, histologic grade, and histologic type. The use of targeted therapy for FoxM1 might be of interest in the prevention of tumor progression in CRC.

High hairy and enhancer of split 1 and low SOX17 immunohistochemical hepatic expression is associated with human biliary atresia Shereen F El-Goday, Dina S El-Azab, Mona A Kandil, Hayam A Aiad, Mostafa M Sira, Mona S Tantawy Egyptian Journal of Pathology 2019 16(1):18-25 Background Early discrimination of biliary atresia (BA) from other causes of neonatal cholestasis is a cornerstone for successful surgical intervention. To date, the exact etiology of BA remains elusive. We aimed to investigate the hepatic expression of hairy and enhancer of split 1 (HES1) and SOX17 in infants with BA compared with non-BA causes of cholestasis. Methods The study included 61 infants with cholestasis in two groups, BA (n=32) and non-BA (n=29). HES1 and SOX17 hepatic expression was evaluated in biliary epithelial cells as proportion×intensity for the total score. Results The frequency of positive HES1 expression was significantly higher in BA (84.8%) compared with non-BA (35.7%). In addition, the HES1 score was significantly higher in BA than in non-BA. The frequency of high intensity staining was significantly higher in BA (50%) compared with non-BA (20%). All patients were positive for SOX17. The SOX17 score was significantly lower in BA compared with non-BA. Furthermore, the occurrence of low-intensity staining was significantly higher in BA (84.4%) compared with non-BA (46.4%). Clay stool, higher gamma glutamyl transpeptidase, ductular proliferation, bile plugs, and portal edema are associated with positive HES1 and low SOX17 expression. Furthermore, abnormal gallbladder is associated with low SOX17 expression. Conclusion Positive HES1 and low SOX17 expression are associated significantly with BA. These results support the potential role of these molecules in the etiopathogenesis of BA.

The impact of microvascular density and CD1a+ tumor-infiltrating dendritic cells on the clinical outcome in papillary thyroid carcinomas Asmaa M Ahmed, Heba E.M El-Deek, Hemat A Mahmoud, Mahmoud R.A Hussein Egyptian Journal of Pathology 2019 16(1):26-35 Background Papillary thyroid carcinoma (PTC) represents 80–85% of all thyroid cancers. Dendritic cells (DCs) are effective antigen-presenting cells that can induce antitumor response. CD1a+ DCs were detected in several tumors but their prognostic role is still controversial. Angiogenesis (reflected as microvascular density, MVD) is a prognostic indicator related to tumor growth. To date, studies about the expression patterns of CD1a+ DCs and MVD in PTC are limited. Patients and methods We immunohistochemically investigated the CD1a+ DCs density and MVD (by CD31) in 91 PTC specimens in comparison to their peritumoral tissue and benign follicular-patterned lesions. Results The CD1a+ DCs and MVD were higher in PTC than benign follicular lesions and peritumoral tissue. The density of CD1a+ DCs was significantly correlated with MVD in PTC. Significant higher density of CD1a+ DCs and MVD was found in PTC having adverse clinicopathologic features: classic morphology, large size, capsular invasion, extrathyroidal extension, recurrence, and advanced clinical stage. Finally, we found that advanced clinical stage (III–IV) and high CD1a+ DCs density were significant predictors for increased hazard of recurrence and metastasis in PTC. Conclusion We can suggest that CD1a+ DCs may contribute to PTC progression and angiogenesis. Whether targeting CD1a molecule could have therapeutic ramifications awaits further investigations.

Evaluating the expression of caveolin-1 immunohistochemistry in differentiating malignant pleural epithelioid mesothelioma from lung adenocarcinoma Noha E Ezzat, Eman S Abusinna, Nevine FH Sidhom Egyptian Journal of Pathology 2019 16(1):36-42 Background To evaluate the efficacy of new marker caveolin-1 (Cav-1) in differentiating between malignant pleural mesothelioma (MPM) and lung adenocarcinoma (LAC) and to compare its results with other well-known markers used to differentiate MPM from LAC. Patients and methods This study is a retrospective one conducted on 150 cases presented with pleural and/or pulmonary lesion and diagnosed by pleural segmental resection or biopsy at Pathology Department, National Cancer Institute, Cairo University, during the period from January 2016 to December 2017. Paraffin blocks were immunostained by Cav-1 using Dakoautostainer. Sensitivity, specificity, positive and negative predictive values, and total accuracy of the marker were calculated. Results Cav-1 achieved a sensitivity of 97.1%, a specificity of 93.75%, a positive predictive value of 93.1%, and a negative predictive value of 97.4%, and total accuracy of 95.3% in the cases diagnosed as MPM. Overall, 45 (66.2%) cases showed cytoplasmic expression in more than 50% (3+) of tumor cells, 20 (29.4%) cases in 5–50% (2+), and only three (4.4%) cases in less than 5% of tumor cells (1+). No significant difference was detected in the Cav-1 expression between well-differentiated and poorly-differentiated cases of malignant mesothelioma (MM) regarding score 3+ immunostaining. Conclusion Cav-1 is an immunohistochemical marker that can be used to differentiate MPM from LAC and can be added to the panel of markers used for such purpose.

Assessment of the concordance between fluorescence in-situ hybridization and immunohistochemistry in evaluating topoisomerase IIα in breast carcinoma Iman Loay, Omnia M Badawy, Tarek EL-Bolkainy, Nesreen H Hafez, Nabil El-Bolkainya Egyptian Journal of Pathology 2019 16(1):43-52 Background Topoisomerase IIα (TOP2A), encoded by TOP2A gene, is a molecular target for anthracycline therapy; hence, it can serve as a predictive or prognostic factor. There are several techniques used for measuring TOP2A status. The relative value of TOP2A gene amplification evaluated by fluorescence in-situ hybridization (FISH) and protein expression analyzed by immunohistochemistry (IHC) is yet unclear in the literature. Aim To evaluate the concordance between FISH and IHC for TOP2A status and to assess their relations with some prognostic clinicopathological parameters. Materials and methods A total of 86 invasive breast cancer paraffin blocks were retrieved from the archives of Pathology Department, National Cancer Institute, Cairo University, and were subjected to IHC, with a cutoff value of 10%, and FISH analysis with TOP2A/centromere enumeration probe 17 ratio of at least two for TOP2A expressions. The concordance between the results of both techniques as well as relations with selected prognostic parameters was evaluated. Results Of 86 invasive breast carcinomas, 43 (50%) revealed TOP2A protein overexpression, whereas 23 (26.7%) cases had TOP2A gene amplification. TOP2A gene amplification was recognized in 16 of 43 TOP2A protein-expressed cases, with 37.2% concordance rate and 0.209 κ statistics. TOP2A gene amplification was significantly correlated with human epidermal growth factor receptor-2 immuno-expressing tumors and with molecular subtypes (P<0.001), whereas TOP2A protein level was correlated with histopathological types (P=0.001). Conclusion Discordance was evident between TOP2A gene amplification and protein expression. However, TOP2A gene amplification has a valuable prognostic influence, whereas protein expression is still a predictive factor useful to guide chemotherapy.

Intraoperative identification of parathyroid tissue: a comparative validity study of frozen section, cytology, and reflected-light diagnostic methods Tarek El-Bolkainy, Ahmed Rabie, Muhammad Zain, Nabil El-Bolkainy Egyptian Journal of Pathology 2019 16(1):53-59 Background Surgery is the main line of treatment for hyperparathyroidism, but preliminary localization of the lesion is essential. This could be accomplished preoperatively by radiographic methods (isotope scans and ultrasonography) or intraoperatively by pathologic methods, namely, frozen section, cytology, and reflected-light microscopy. Aim To compare the diagnostic accuracy of the intraoperative pathologic methods when used singly or combined. The study was done on 30 (10 parathyroid tissue and 20 nonparathyroid tissue) tissue samples, obtained from nine patients. Modifications were made on a monocular microscope to allow transmitted-light, reflected-light, and digital photography. Results When used alone, the diagnostic accuracy was 96.6% for frozen section, 86.6% for cytology, and 80% for reflected-light microscopy. The combined use of cytology with reflected-light microscopy increased the diagnostic accuracy to 93.3%, with good concordance with the accuracy of frozen section combined with cytology (κ ratio 0.651). Diagnostic errors were mainly owing to the difficulty to differentiate thyroid from parathyroid tissue. Conclusion In specialized centers, frozen section combined with cytology is the method of choice for the intraoperative diagnosis of parathyroid tissue. Conversely, in developing countries, where frozen section equipment is usually not available, combination of reflected-light microscopy and cytology is a good, inexpensive, rapid and effective alternative. However, proper training is needed for these methods to ensure an accurate diagnosis.

Immunohistochemical expression and prognostic significance of Mortalin in invasive breast carcinoma of no special type Abd El Naby S Mohamed, Mohamed I Shaban, Aiat S Hemida, Moshira M Abd El Wahed, Soha A Moustafa Egyptian Journal of Pathology 2019 16(1):60-69 Objectives The objective of this study was to evaluate the immunohistochemical expression and prognostic significance of Mortalin in invasive breast carcinoma of no special type. Background Breast cancer (BC) is the most common cancer in Egypt and worldwide. It is the leading cause of cancer-related death among female individuals. Mortalin is a stress chaperone enriched in many cancers and has been implicated in carcinogenesis. Patients and methods This study was carried out on 60 cases of invasive ductal carcinoma of no special type, 25 adjacent ductal carcinoma in situ and 15 cases of normal breast tissue. Immunohistochemical staining for Mortalin was applied on the archival formalin-fixed paraffin-embedded blocks. Staining was assessed semiquantitatively taking staining extent and intensity into consideration. Results were correlated with the available clinicopathologic parameters, immunohistochemical subtypes of BC and survival. Results Mortalin cytoplasmic expression was higher in BC (76.7%) (46/60) than in either adjacent ductal carcinoma in situ (56%) (14/25) or in normal breast tissues (26.7%) (4/15). Statistical analysis revealed the association of Mortalin expression with high tumor grade (P<0.02), advanced American Joint Committee on Cancer stage grouping (P<0.000), late tumor T stage (P<0.03), positive lymph node N stage (P<0.000) and poor Nottingham Prognostic Index (P<0.000). Furthermore, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/neu statuses and immunohistochemical subtypes of BC showed a significant relationship with Mortalin expression. Conclusion This study showed that Mortalin plays an important role in the progression of BC, and overexpression of Mortalin in BC has poor prognostic role evidenced by its association with poor prognostic parameters such as high-grade tumors, advanced stage, and positive lymph nodes. Hence, Mortalin may be used as a prognostic marker and therapeutic target in BC.

Comparative study of paired box gene 8, cytokeratin 7, and cytokeratin 20 in differentiating the ovarian from nonovarian carcinoma cells in peritoneal effusions Azza M Rizk, Bassma ElSabaa, Mohammed Farouk, Reham Abdel Haleem, Eman S Elsawy Egyptian Journal of Pathology 2019 16(1):70-78 Background In female patients, ovarian carcinoma is considered a common cause of malignant peritoneal effusions that shows a good response to chemotherapy, an issue that mandates quick and accurate diagnosis of those cases. PAX8 is a cell lineage factor that plays a crucial role in the morphogenesis of the kidney, thyroid gland, and Müllerian system. It is expressed in 95–100% of ovarian carcinomas in tissue sections. Recently, it was suggested as a potential marker for the diagnosis of ovarian carcinomas in effusions. Aim This study aimed at assessing the role of CK7, CK20, and PAX8 in differentiating ovarian from nonovarian carcinomas in peritoneal effusions. Patients and methods Immunocytochemical evaluation of CK7, CK20, and PAX8 expression in 40 cell blocks of malignant peritoneal effusion samples was carried out. In addition, the assessment of PAX8 level using double-antibody sandwich enzyme-linked immunosorbent assay technique in the serum of the included cases was also carried out. Results Of the studied 40 cases, 21 (52.5%) proved to be ovarian carcinomas, whereas 19 (47.5%) were nonovarian. Diffuse CK7 expression (scores 3, 4) was significantly detected more frequently in effusions from ovarian than from nonovarian carcinomas. In contrast, CK20 expression tended to be more prevalent in effusions of nonovarian than in those of ovarian origin; however, this was statistically insignificant. PAX8 expression was significantly more frequent in effusions from ovarian carcinomas than from nonovarian carcinomas. Sensitivity and specificity of PAX8 in the diagnosis of ovarian carcinoma was higher than that of CK7, while a combination of both CK7 and PAX8 immune scores using a generated regression equation was the most specific. In contrast, serum PAX8 level was statistically higher in ovarian more than in nonovarian carcinoma cases. Conclusion PAX8 is a useful immune marker for the diagnosis of ovarian carcinoma in peritoneal effusions. However, the combination of both CK7 and PAX8 using a generated regression equation increases the specificity of diagnosis. PAX8 serum level is a potential serum marker in diagnosing ovarian carcinomas.

Stromal androgen receptor expression in prostate cancer in relation to clinicopathological parameters Farida A.A Shokeir, Mona Y.Y Abd Allah, Amro A El-Karef, Mohamed Abdelhamid, Tawakol G El-Sayed Egyptian Journal of Pathology 2019 16(1):79-88 Background Prostate cancer (PCa) is one of the most commonly diagnosed male tumors all over the world. Most studies have concentrated upon the established role of epithelial androgen receptor (AR) expression in PCa, but the role of stromal AR expression is still not completely understood. Aim To assess immunohistochemical expression of stromal AR and investigate its relation to the PCa grade (according to the new contemporary advances in Gleason score/grading system) and other clinicopathological parameters. Materials and methods This is a retrospective study performed on 65 cases of PCa. All cases were immunohistochemically stained for AR to assess its stromal expression using the Allred score applied for estrogen receptor (ER) and progesterone receptor (PR) in the breast. The results were recorded for statistical analysis. Results Stromal AR was significantly related to the percentage of PCa in the specimen (P=0.003), tumor grade (P=0.001), perineural invasion (P=0.041), and cancer stage (P=0.001). On the contrary, stromal AR expression showed statistically insignificant relation with patients’ age (P=0.231), diabetes mellitus status (P=0.073), preoperative prostate-specific antigen level (P=0.202), digital rectal examination result (P=0.421), weight of the prostate (P=0.083), tumor size (P=0.209), and lymph node metastasis (P=0.411). Moreover, using Spearman’s correlation, there was a highly statistically significant correlation between stromal AR score and both Gleason grade/score (P<0.0001) and TNM/American Joint Committee on Cancer stage (P<0.0001). Conclusion AR expression in prostatic cancer stroma may have protective value against cancer progression.