Purpose The present study aimed to compare between two techniques used for cervical screening: conventional Pap smear and liquid-based cytology (LBC). Patients and methods This study included 150 women referred from the early detection unit to the Cytopathology Unit, Pathology Department, NCI, Cairo University, for detection of cervical precancerous lesions. The ectocervix and endocervix were sampled using cytobrush, and the material was smeared on two glass slides and prepared for conventional smears. Rovers cervix-brush was used to collect samples for SurePath LBC, where the brush head was detached and dropped in the specific preservative-containing vial. Cytologic reporting was done according to the New Bethesda System 2014 for both preparations. Both qualitative and numerical data were calculated. Fleiss’ kappa was used to measure the agreement between both techniques. P value was calculated when required, which is considered significant if less than 0.05. Results Of the 150 included cases, 117 (78%) were satisfactory for evaluation with conventional preparation (CP), whereas 147 cases were satisfactory using liquid-based technique. The difference was found to be statistically significant. Endocervical cells were detected in 53/117 (45.3%) satisfactory cases of CP and in 84/147 (57.1%) satisfactory cases of LBC. Among the 117 satisfactory cases by both methods, CP can detect 49 (42%) cases with squamous or glandular lesions. On the contrary, in LBC, 41 (35%) cases showed epithelial abnormalities. The rate of atypical squamous cells of undetermined significance was lower in LBC (3%) compared with CP (7%). The glandular lesions were better detected in CP when compared with LBC (24 and 18%, respectively). The diagnosis of both preparations was different in 18 (12%) cases. In three (16.7%) cases, the diagnosis was upgraded by liquid based preparation (LBP), whereas a lower grade was given by LBP in 15 (83.3%) cases. Conclusion The rate of unsatisfactory cases was significantly reduced when LBC was used. LBC can be used for cervical cancer screening as CP, where there was a good agreement between their results.

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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.

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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.

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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.

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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.

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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.

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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.

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Background Diffuse large B-cell lymphomas (DLBCLs) are a heterogeneous group with variable prognosis. Double-expressor (DE) and triple-expressor (TE) lymphomas have emerged as uncommon indistinct subgroups of high-grade B-cell lymphomas that may have prognostic value. This study aimed at evaluating the role of immunohistochemistry (IHC) in the detection of DE and TE lymphomas as well as correlating them with clinicopathological parameters. Materials and methods This is a retrospective study conducted on 100 cases of DLBCL. Tissue microarray blocks were constructed and immunostained with antibodies for MYC, BCL2, BCL6, CD10, MUM1, and P53 to determine the germinal center, activated B cell, DE, and TE phenotypes. Results We have found a statistically significant correlation between both DE and TE lymphomas and reduced disease-free survival (P=0.03) as well as with nodal location (P=0.006). No statistically significant correlation was found with clinicopathological parameters such as age, sex, stage, international prognostic index score, or response to therapy. No statistically significant difference was found between DE and TE groups. Conclusion DE and TE lymphomas can be considered as poor prognostic subgroups of DLBCL associated with reduced disease-free survival. Our study stresses the value of immunohistochemistry in the detection of such adverse groups of DLBCL.

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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.

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Background The overlapping phenotypic features between the reactive mesothelial cells and the malignant ones pose a major diagnostic challenge in routine cytology practice. Questions have been raised about the privilege of cell block (CB) over conventional smears. There is a lot of controversy about the best immunohistochemical panel that could help in differentiation. Aim This research attempts to compare between the cellular morphology results in conventional smears and CB method. It seeks to address the reliability of calretinin, p-16, and claudin (CL)-4 immunohistochemistry use as an aid to differentiate between reactive and malignant mesothelial cells as well as carcinomatous ones in serous effusion samples. Materials and methods This retrospective study was conducted on 46 (23 pleural effusion and 23 peritoneal one) cases of effusion fluids. Conventional smears and paraffin-embedded blocks sections were examined and score tabulated. Calretinin, p-16, and CL-4 immunohistochemical expression was studied and correlated with available clinical and cytological data. Results Of the 46 cases studied, there were 25 (54.3%) cases of metastatic adenocarcinoma, 10 (21.7%) cases of mesothelioma, and 11 (23.9%) cases of reactive effusions. Our studied cases showed that 24/46 (52.2%) CBs had cytomorphologic criteria of the diagnostically superior group compared with 22/46 (47.8%) smears. The group of diagnostically adequate material was represented by 22/46 (47.8%) CBs and 24/46 (52.2%) smears. Considering calretinin immunocytochemistry, regarding detection of mesothelial cell lesions, sensitivity was 52.4%, specificity was 100%, positive predictive value was 100%, negative predictive value was 71.4%, and total accuracy was 78.26%. p-16 as a differentiating marker between mesothelioma and atypical reactive mesothelial cells has a sensitivity of 45.5%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 62.5%, and total accuracy of 71.43%. CL-4 being a marker of metastatic adenocarcinoma was used to differentiate it from mesothelioma; CL-4 has 96% sensitivity, 60% specificity, 85.7% positive predictive value (PPV), 85.7% negative predictive value (NPV), and total accuracy of 85.7%. When a panel of two markers was assessed as an ancillary technique to cytomorphology, the combination of calretinin negativity and CL-4 positivity had the best results in diagnosing cases of metastatic adenocarcinoma with 96% sensitivity, 80.9% specificity, and 89.1% total accuracy. A panel of three markers was applied to differentiate benign from malignant effusions and for subclassifying malignant ones into mesotheliomatous versus metastatic. Regarding benign reactive effusions, the studied panel had a sensitivity of 27.3%, a specificity of 100%, and total accuracy of 82.6%. Considering mesothelioma cases, the panel has 30% sensitivity, 88.9% specificity, and 76.1% accuracy. When the panel was applied to detect metastatic cases, it revealed 44% sensitivity, 85.7% specificity, and 63% total accuracy. Conclusion The findings of this study suggest that CB use is an added privilege in serous effusion cytology. Immunohistochemical panel of calretinin, p-16, and CL-4 is beneficial in differentiating benign from malignant effusions and for subclassifying malignant ones into mesotheliomatous versus metastatic.

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Breast cancer (BC) is considered as one of the most frequent cancers worldwide. GATA3 plays a crucial role in promoting proliferation and differentiation in many tissues including breast. Loss of GATA3 expression in BC has been associated with aggressive tumors and poor prognosis. Androgen receptor (AR) has been reported to be involved in differentiation, development, and regulation of breast cell growth. The aim of this study was to investigate the immunohistochemical expressions of GATA3 and AR and their relationships with different clinicopathological features and molecular phenotypes and to further evaluate their prognostic significance. Immunohistochemical expressions of GATA3 and AR were evaluated in 61 formalin-fixed and paraffin-embedded tissue specimens of invasive duct carcinoma. Positive GATA3 immunostaining was detected in 54.1% of cases and showed significant associations with lower tumor grade (P=0.007), estrogen receptor (ER)-positive expression (P=0.000), progesterone receptor-positive expression (P=0.001), and good and moderate Nottingham prognostic index (P=0.012). No significant relationship was found between GATA3 expression and other clinicopathological parameters. Positive AR expression was detected in 60.7% of cases and showed positive significant associations with lower tumor grade (P=0.005), ER-positive expression (P=0.0001), progesterone receptor-positive expression (P=0.001), and good and moderate Nottingham prognostic index (P=0.011). No significant relationship could be found between AR expression and other clinicopathological features. Higher rates of positive GATA3 and AR expressions were observed in luminal A and luminal B phenotypes, but negative expressions of GATA3 and AR were observed frequently in HER2 and triple-negative breast cancer subgroups (P=0.001 and 0.001, respectively). To determine the immunoprofile of the examined tumors, cases were stratified according to the joint expression status of GATA3 and AR. This study has found a highly significant positive correlation between the expressions of GATA3 and AR (r=0.99, P<0.0001). Univariate survival analyses demonstrated that cases expressing positive GATA3 and AR had a significantly longer relapse-free survival and better clinical outcomes than those with negative expressions (log-rank P=0.0000 and ˂0.0001, respectively). Cox multivariate regression analysis has selected ER (P=0.015), stage (P=0.014), AR (P=0.003), and combined GATA3/AR immuonoexpressions (P=0.048) as independent prognostic indicators. Altogether, our findings suggest that AR and combined GATA3/AR immunoexpressions can serve as independent good prognostic biomarkers in BC.

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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.

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Background Prostatic carcinoma remains one of the most prevalent cancers among men and a major source for morbidity and mortality. Fascin-1 is significantly elevated in advanced stage and lymph node metastasis and has great prognostic values in head and neck squamous cell and colorectal cancers. Ki-67 expression is the tissue biomarker with the most consistent association with the clinical outcomes of prostatic carcinoma. Aim To evaluate the immunohistochemical expression pattern of Fascin-1 and Ki-67 and correlate the results with clinicopathological parameters. Materials and methods A retrospective study was carried on 80 cases of prostatic carcinoma. Immunohistochemical staining with monoclonal Fascin-1 and Ki-67 antibody was performed. Results Fascin-1 expression was positive in 90% of cases of prostatic carcinoma. There was a statistical relationship between Fascin-1 expression and prostatic-specific antigen level, Gleason score, lymphovascular and perineural invasion. Ki-67 expression was positive in 98.75% and showed positive statistical relationship with Gleason score and lymphovascular and perineural invasion. A positive relationship was found between Fascin-1 expression and Ki-67 expression in tumor cells. Conclusion Fascin-1 and Ki-67 expression tend to increase with more aggressive prostatic carcinoma. They may be used as a prognostic marker to predict poor outcome in patients with prostatic carcinoma.

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Background Although cytological interpretation of classic pulmonary neuroendocrine tumors (NETs) is straightforward, their identification remains a diagnostic challenge in daily practice, especially if cytomorphological features are unclear. The currently used immunostaining panel has some limitations. insulinoma-associated protein 1 (INSM1) is a transcription factor that is reported in different NETs. The aim of the current study was to identify INSM1 expression in cytological materials of lung NETs, to compare its performance with that of the currently used markers and to compare the expression in primary and corresponding metastatic NETs. Materials and methods This retrospective study included 40 cytological samples of primary pulmonary NETs and nine metastatic extrapulmonary materials of the same patients as well as 20 samples of non-NETs (control group). Image-guided fine-needle aspiration was performed. Cell block sections were stained for INSM1, synaptophysin, CD56, and chromogranin A. For all markers, at least 1% positive cells were considered positive. Diffuse/strong positive was reported if at least 50% of the cells were detected at low power magnification. Focal/weak positivity was defined if less than 50% of tumor cells were positive but not easily identified at low power. Results INSM1 was positive in 92.5% (37/40). The sensitivity for small-cell lung carcinoma, large-cell neuroendocrine carcinoma, and carcinoid was 92.6, 91.7, and 100%, respectively. No significant statistical difference was identified regarding expression in various NET subtypes (P>0.05). INSM1 was negative in all non-NETs. The INSM1 sensitivity was similar to CD56 sensitivity but more than that of synaptophysin and chromogranin. The INSM1 specificity was higher than those of CD56 and chromogranin A and equal to synaptophysin. The INSN1 sensitivity was similar to the sensitivity of the combined conventional markers as a group with a superior specificity. INSM1 staining in the nine metastatic NETs was matched up to their primary tumors. Conclusion INSM1 combined high sensitivity, specificity, and accuracy when compared with the currently used markers. Nuclear INSM1 expression is easier and faster to interpret than the cytoplasmic or membranous expression of the other markers. It should be used in neuroendocrine marker panels. INSM1 staining was retained in all metastatic sites.

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Background Cytomorphological and immunohistological characteristics of lung adenocarcinoma (LAC) and papillary thyroid carcinoma can overlap. BRCA1-associated protein 1 (BAP1) mutations influence the development of multiple tumors and are associated with poor prognosis. Although extremely rare in LAC, BAP1 status in sporadic thyroid carcinoma is not determined. Aim To screen BAP1 mutation in thyroid carcinomas, and compare it with LAC, in an attempt to determine BAP1 clinicopathological significance and the practicability of BAP1 immunohistochemistry in differentiating problematic cases. Materials and methods BAP1 immunoexpression and clinicopathological correlations were analyzed in LACs (n=28), thyroid papillary carcinoma (n=49), and its aggressive continuum, that is, high-grade poorly differentiated and anaplastic thyroid carcinomas (n=7). Results Loss of BAP1 nuclear localization/function was more likely in LACs (7.1%) compared with papillary thyroid carcinomas (28.6%) (P=0.026) and high-grade thyroid carcinomas (71.4%) (P=0.001) (odds ratio=6.6, confidence interval=1.4–31, P=0.008). In BAP1-negative thyroid cancer, loss of nuclear staining was observed in the neoplastic cells and adjacent thyroid tissue. In LACs and thyroid papillary carcinomas, BAP1-deficit tumors were associated with lymph node metastasis (P=0.04 and 0.02, respectively), pleural extension (P=0.008), and extrathyroid extension (P=0.04). Conclusion The mutation of BAP1 in thyroid cancer may occur early and seems more common than lung cancer. Accordingly, BAP1 immunohistochemistry may be used as an ancillary marker to differentiate lung and thyroid masses with equivocal morphology and overlapping immunohistochemistry. BAP1 loss/mutation promotes tumor invasion and metastasis.

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Background Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a part of the mitochondrial heat shock proteins. TRAP1 expression is associated with resistance to apoptosis and therapeutic agents in multiple cancers. This study assessed TRAP1 and p53 expression in epithelial ovarian neoplasms and their association with clinicopathological parameters. p53 is a tumor-suppressor gene and key regulator of glycolysis in neoplastic cells but is mutated in tumors. Our aim was to study TRAP1 and p53 expression in epithelial ovarian neoplasms and their relation to prognostic parameters. Material and methods TRAP1 and p53 expression was evaluated in 78 cases of epithelial ovarian tumors by immunohistochemistry. Results TRAP1 expression was detected in 27 (34.62%) cases. TRAP1 expression was significantly higher in malignant cases compared with benign and borderline ones (pairwise P<0.001 and P=0.02, respectively). Within the carcinoma cases, TRAP1 was significantly associated with high tumor grade (P=0.003) and advanced FIGO stage (P=0.01). No significant relation was found between TRAP1 in malignant cases and the histologic tumor type. Nuclear expression of p53 was detected in 25 (32.1%) cases, all malignant, and it was not expressed in any of the studied benign and borderline ovarian tumors. p53 expression in malignant group was statistically higher than in benign and borderline groups (pairwise P<0.001). Within epithelial ovarian cancer (EOC) cases, a statistically significant relation between p53 expression and the histopathological type (P>0.001) and advanced FIGO stage (P=0.02) was found. A positive correlation between TRAP1 and p53 expression in epithelial ovarian tumors was detected using Pearson correlation coefficient (r=0.463; P<0.001). Conclusion TRAP1 and p53 are associated with EOC carcinogenesis and poor prognosis. These molecules may have a therapeutic role in EOC.

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Background Thyroid carcinoma ranks as the most common among malignancies of endocrine organs, and a rapid increase in its incidence has been observed over the years. Assessment of epithelial cell adhesion molecule (EpCAM) and epidermal growth factor receptor (EGFR) immunopositivity in papillary carcinoma thyroid was conducted, and expression was correlated with the clinicopathological parameters. Materials and methods Immunohistochemical detection of EpCAM and EGFR was investigated in 33 thyroidectomy specimens with papillary carcinoma and 10 cases of hyperplastic thyroid nodule. The association between those markers was studied, besides their correlation with clinicopathological parameters. Results Both EpCAM and EGFR showed weak or low expression in hyperplastic nodule compared with higher expression in papillary carcinoma (P<0.001). In cases showing extrathyroid extension, lymph node metastasis, distant metastasis, and advanced TNM stage, EpCAM and EGFR were significantly correlated (P<0.001, 0.01, 0.01, <0.001, 0.02, <0.001, 0.02, 0.02, and <0.001, respectively). Conclusion Combined expression of EpCAM and EGFR may be related to papillary thyroid carcinogenesis, which could be used as therapy for cancer management.

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Background Oral malignancy includes a group of neoplasms affecting any district of the oral cavity, salivary glands, and pharyngeal regions. Notwithstanding, this term has a tendency to be utilized conversely with oral squamous cell carcinoma (OSCC), which represents the most incessant of every oral neoplasm. It is evaluated that a greater than of 90% of oral neoplasm are OSCC malignancies. The Bcl-2 protein is the encoding result of Bcl-2 proto-oncogene. The overexpression of Bcl-2 protein assumes an imperative part in apoptosis protection in many tumors, including head and neck squamous cell carcinoma. Aim/objectives This study was conducted to scope and find out the possible role of Bcl-2 in the biological behavior of OSCC. Methods A total of 20 OSCC cases were immunohistochemically examined for expression of Bcl-2. Results and conclusions There was significant difference among grades of OSCC regarding Bcl-2 expression. A significant correlation between Bcl-2 expression and clinical staging, nodal infiltration, as well as distant metastasis was observed. We concluded that Bcl-2 may be used as a prognostic factor for OSCC and may aid in decisions on cancer diagnosis and therapy.

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Background Gastric carcinoma is the fifth most common malignancy in the world and one of the cardinal causes of cancer-related deaths. Although there is much progress in diagnosis and treatment approaches, the prognosis of gastric cancer cases is still disappointing. Therefore, recognition of other prognostic markers might qualify a better prognostic differentiation and more powerful therapy. Aim To evaluate CDX2 and cyclooxygenase-2 (COX2) immunohistochemical expression in gastric carcinoma cases, and whether these markers are helpful in estimating prognosis in correlation with other clinicopathological parameters. Materials and methods The study included 50 specimens of surgically resected gastric carcinomas in which the expression of CDX2 and COX2 was assessed. The results were compared statistically with χ² and Fisher exact text. Results CDX2 protein is overexpressed in more differentiated tumors with less lymphovascular invasion and less nodal metastasis. However, COX2 shows significant association with high-grade tumors and higher depth of invasion. CDX2 expression is negatively correlated with COX2 expression in gastric carcinoma. Conclusion The results of this study suggest that CDX2 and COX2 may be good prognostic tools for gastric carcinoma. Using these markers as a target might eventually become a specific treatment of choice.

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Background Cancer is considered a stem cell disease. Many stem cell markers are recently well known to have main roles in carcinogenesis and tumor progression. Aldehyde dehydrogenase 1A1 (ALDH1A1) is a stem cell marker that thought to have a role in many cancers. This study aimed to evaluate the expression of ALDH1A1 in different molecular types of breast invasive ductal carcinomas (NOS), and its relation to clinicopathological data. Materials and methods This is a retrospective study carried out on 40 cases of NOS of the breast. The cases were collected from archives of Early Cancer Detection Unit, Benha Faculty of Medicine and Pathology Department, International Medical Center, between the years 2007 and 2013. Previously estrogen receptor, progesterone receptor, Her2/neu and Ki-67 stained slides were reevaluated for each case. Both tumoral and stromal expression of ALDH1A1 was also evaluated for each case. Results A significant positive correlation of ALDH1A1 tumoral expression was observed in patients with age more than 55 years (P<0.05), higher tumor grade (P<0.05), large tumor size (T) (P<0.05), lymph node metastasis (P<0.01), distant metastases, and advanced TNM stage (P<0.05). A significant association of tumoral ALDH1A1 with estrogen receptor and progesterone receptor negativity was noted (P<0.05) while the expression of ALDH1A1 in tumor cells appeared more frequently in Her2/neu-positive cases (P<0.05). Expression of ALDH1A1 in stromal cells correlated inversely with the presence of distant metastasis and advanced tumor stage (P<0.05 for both). Tumoral ALDH1A1 expression showed inverse highly significant correlations (P<0.0001) with patient’s survival. Increased stromal expression of ALDH1A1 showed a significant relation to disease-free survival and overall survival (P<0.05). Tumoral ALDH1A1 expression correlated inversely with the overall survival and disease-free survival of luminal A and luminal B cases (P<0.05 for all). Conclusion ALDH1A1 may have a dual role in NOS progression. Also, ALDH1A1 could be used to predict chemoresistant cases among different molecular subtypes. Induction of stromal ALDH1A1 expression could be a possible therapeutic target in the future to suppress tumor progression.

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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.

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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.

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Background Breast cancer (BC) is a major global problem. Despite the recent guidelines used for BC treatment, still complete cure need of BC is unmet. Therefore, finding a new prognostic factor can be valuable for the management of BC. Toll-like receptors (TLRs) have gained a lot of interest in BC research owing to their role in tumor progression. Aim The aim of this study was to evaluate the immunohistochemical expression of both TLR9 and tumor necrosis factor receptor-associated factor (TRAF) 6 in invasive duct carcinoma of breasts among women and to correlate their expression with the clinical data of the patients. Materials and methods Immunohistochemical analysis of the expression of TLR9 and TRAF6 was analyzed on paraffin-embedded sections from 67 patients with invasive ductal carcinoma of the breast. Results TLR9 and TRAF6 were positive in 62.7 and 35.8% of cases, respectively. Both TLR9 and TRAF6 expressions were significantly associated with nodal metastasis, tumor stage, and Nottingham prognostic index. Only TLR9 expression was significantly correlated with estrogen and progesterone receptor expressions (P=0.0001 and 0.010, respectively). Moreover, it is associated with triple-negative BC cases (P=0.014). Our results showed an association between TLR9 and TRAF6 expressions (P<0.0001). All cases that were negative for TLR9 were also negative for TRAF6. On the contrary, 18 (41.9%) of TLR9-positive cases showed TRAF6 negativity. Conclusion Both TLR9 and TRAF6 may have a role in BC invasion and prognosis. Moreover, TRAF6 was not regulated by TLR9, and its upward stream pathway is suggested to be either by other TLRs member or different molecules.

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Background Clinicopathological features of basal-like breast cancer (BLBC) in African-American women have been extensively studied. Comparatively, less is known about these tumors in patients from countries in the North African region. The aim of this study was to assess the frequency and clinicopathological characteristics of BLBC in Egyptian patients in comparison with British patients. Patients and methods Tissue microarray blocks were constructed from primary invasive breast cancers from 321 Egyptian and 527 British patients with BC. Sections were stained immunohistochemically with estrogen receptor, progesterone receptor, epidermal growth factor receptor 2, CK19, CK14, EGFR, CK5/6, P53, and Ki-67. BLBC phenotype was identified by the lack of staining of estrogen receptor, progesterone receptor, and epidermal growth factor receptor 2, and positive staining for any of the CK14, CK5/6, and/or EGFR. Results The rate of BLBC phenotype was higher in Egyptian cohort (21%) than the British cohort (13%). BLBC tumors from both Egyptian and British patients were significantly associated with tumors of higher histopathological grade (P<0.001 and <0.001, respectively), higher proliferation rate (P<0.001 and 0.001, respectively), and higher rate of P53 expression (P<0.001 and <0.001, respectively). Compared with the British patients with tumors, BLBC in Egyptian women were significantly of larger tumor size (P<0.001) and were associated with more advanced lymph node stage (P<0.001). Conclusion BLBCs occurred more frequently in Egyptian patients compared with British women and are characterized by unfavorable biological features, akin to BLBC in African-American women. These findings warrant further studies to unravel the genetic background of BLBCs and whether their aggressive features are related to ethnic origin or other multifactorial and environmental variables.

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Background The incidence of endometrial carcinoma among Egyptian women has increased in the past few years. This work was performed to evaluate the role of autophagy marker Beclin-1 in endometrial carcinoma type I and correlate it with progesterone receptor (PR) and Bcl-2 expression. Materials and methods This retrospective study included 30 cases of endometrial carcinoma type I, eight cases of endometrial hyperplasia with atypia, and seven cases of endometrial hyperplasia without atypia. Cases were collected from archives of Pathology Department and Early Cancer Detection Unit, Faculty of Medicine, Benha University, through the years 2011 to 2017. Beclin-1, Bcl-2, and PR immunohistochemichal staining was performed on all cases, and the patterns of expression were analyzed. Results Beclin-1 was expressed in 36.7, 62.5, and 71.5% of endometrial carcinoma, endometrial hyperplasia with atypia, and hyperplasia without atypia, respectively. This showed a statistically significant difference (P<0.05). Bcl-2 expression was positive in 53.3, 25, and 14.5% of endometrial carcinoma, endometrial hyperplasia with atypia, and hyperplasia without atypia, respectively, with statistically significant difference (P<0.05). Positive PR immunoreactivity was reported in 40% of endometrial carcinomas, 75% of endometrial hyperplasia with atypia, and 85.5% of hyperplasia without atypia (P<0.05). Both Beclin-1 and PR expressions were significantly increased in correlation with decreased Bcl-2 expression in carcinoma cases (P<0.01). Conclusion Combined estimation of PR and Beclin-1 is a good prognostic marker for endometrial carcinoma type 1. Combination of progestins with proautophagic substances could be used in resistant cases to improve results of treatment.

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