Evaluation of the Prognostic Value of Solute Carrier Family 34 Member 2 "SLC34A2" in Papillary Thyroid Carcinoma: An Immunohistochemical Study.

BACKGROUND: Papillary thyroid carcinoma (PTC) usually has an indolent clinical course, yet a subset of patients might show an aggressive course. Thus, better stratification of at-risk patients is mandatory for proper management. Solute carrier family 34 member 2 (SLC34A2) is an independent prognostic indicator in several cancers. However, only a few studies have been conducted to evaluate the prognostic value of SLC34A2 in PTC, with none of them assessing its immunohistochemical (IHC) expression in a large cohort of patients with PTC or exploring its possible relationship with tumor progression. Aim of the Study. We aimed to evaluate the IHC expression of SLC34A2 in a large series of PTC patients, correlate its expression with established clinicopathological factors, and find any possible relationship between this marker and patient prognosis. Material and Methods. A total of 476 samples (including 238 samples of PTC and 238 samples of normal thyroid tissue) collected between 2002 and 2005 were extracted from the archives of the Pathology Lab, Ain Shams University Hospitals. IHC analysis was performed using an anti-SLC34A2 antibody. Follow-up data were obtained. RESULTS: High SLC34A2 expression significantly correlated with important adverse clinicopathological parameters of PTC-i.e., late tumor stage, positive extrathyroid extension, tumor size  >  4 cm, and age  ≥  55 years (p ≤ 0.001 for each). Kaplan-Meier analysis revealed that high SLC34A2 expression significantly correlated with shorter disease-free survival (DFS; p = 0.005), but not with overall survival (p = 0.111). Multivariate analysis showed SLC34A2 to be an independent prognostic factor affecting DFS. CONCLUSIONS: High SLC34A2 IHC expression correlated with adverse clinicopathological prognostic parameters. Furthermore, SLC34A2 was identified as an independent factor for DFS that could serve to improve risk stratification of PTC patients for better management.

Diagnostic Utility of BAP1, EZH2 and Survivin in Differentiating Pleural Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia: Immunohistochemical Study.

Background: Epithelioid mesothelioma (EM) is the commonest subtype of malignant pleural mesothelioma. Its histopathological discrimination from reactive mesothelial hyperplasia (RMH) could be challenging. Thus, an immunohistochemical panel is mandatory for better discrimination. BAP1 is a newly identified diagnostic marker whose loss is specific to malignant mesothelioma. EZH2 overexpression is reported in different cancers, but its relation to BAP1 in malignant mesothelioma has not been fully understood. Survivin expression is said to be significantly higher in EM than in non-neoplastic pleural tissue, but its diagnostic utility as an immunohistochemical marker has not been thoroughly investigated in this field. To the best of our knowledge, no previous studies have been conducted to assess the diagnostic accuracy of the combined use of these three nuclear markers (BAP1, EZH2 and Survivin) in discriminating pleural EM from RMH. Methods: This retrospective study includes two groups: 81 cases of pleural EM and 67 cases of RMH, retrieved from the archives of Pathology Department of Ain Shams University Hospitals and Ain-Shams University Specialized Hospital during the period from January 2016 to December 2019. An immunohistochemical study was performed using BAP1, EZH2 and Survivin antibodies. Results: There were highly statistically significant relations between study groups as regards the studied markers (p = 0.001 for each). The specificity was 100% for all combinations of immunohistochemical markers. Sensitivity of any combination of the immunohistochemical markers used in this study was found to be higher than the sensitivity of any of these markers used individually. The combination of all three markers showed the highest diagnostic accuracy (95.9%) and the highest sensitivity (92.6%). However, the combination of Survivin and EZH2 yielded the same diagnostic accuracy and sensitivity. Conclusion: Adding EZH2, Survivin and BAP1 to the diagnostic IHC panel for differentiating pleural EM and RMH could enhance diagnostic sensitivity. Moreover, Survivin is a potentially promising marker in this context, especially when combined with EZH2.

Evaluation of crypt apoptotic bodies and apoptotic indices in pediatric celiac disease by routine staining and H2AX immunostaining.

Celiac disease (CD) is an immune-mediated disorder with premature apoptosis occurring along the entire crypt-villous axis. H2AX is the end product of the intrinsic apoptotic pathway. This is the first study to assess apoptotic body counts (ABC) by H&E and apoptotic indices (AI) by immunohistochemistry (IHC) in pediatric CD. The aim of the current study was to evaluate ABC in pediatric patients with CD prior to and following institution of a gluten free diet (GFD). Sixty-three pediatric endoscopic duodenal samples were assessed and divided into three groups. A total of 21 samples from treatment naïve CD patients, 21 from the same patients after instituting a GFD, and 21 from non-celiac patients as a control group. Histopathological evaluation of ABC by H&E, and immunohistochemistry assessment of apoptotic indices (AI) by H2AX antibody were performed. The mean maximum ABC and AI were significantly higher in treatment naïve CD than in GFD and control samples. These values were also significantly higher in treatment naïve Marsh 3C (flat) than in Marsh 1, 2, 3A, and 3B (non-flat) CD cases. GFD samples with persistent flat lesions had significantly higher ABC and AI than GFD non-flat cases. ROC analysis of the mean maximum ABC and AI of treatment naïve CD cases had a statistically significant predictive potential for persistent villous atrophy at a cut-off level ⩾6.61 (P = 0.008) and ⩾105.4 (P = 0.003), respectively. Histopathological evaluation of crypt apoptotic bodies could provide predictive potential for continued villous atrophy following GFD.

Implications of androgen receptor and FUS expression on tumor progression in urothelial carcinoma.

Androgen receptor (AR) interact with many pathways involved in bladder cancer development and progression. FUS (fused in liposarcoma), a multifunctional protein essential for different cellular processes, has been demonstrated as a key link between androgen receptor signaling and cell-cycle progression in prostate cancer but has not been examined in urothelial carcinoma (UC) despite an intimate association between prostate and bladder carcinogenesis. AIM: To examine the immunohistochemical expression of AR and FUS in urothelial carcinoma in relation to prognostic parameters and to extrapolate any possible link between the expression of both markers and tumor progression. STUDY DESIGN: Retrospective study using immunohistochemical staining for AR and FUS on (88) cases of urothelial carcinoma. RESULTS: AR shows statistically significant relations with late tumor stage, high tumor grade, and non-papillary tumor pattern. On the other hand, FUS expression correlates with early tumor stage, low tumor grade and papillary pattern. An inverse relation is found between AR and FUS expression (p=0.001). Cases with high AR IHC expression show statistically significant shorter OS, RFS and PFS compared to cases with low AR expression. Cases with high FUS IHC expression reveal statistically significant longer OS, RFS and PFS compared to cases with low FUS expression. CONCLUSION: FUS expression is associated with favorable prognostic parameters of UC. A possible interaction is suggested between FUS and AR pathways involved in urothelial cancer progression. Manipulating FUS levels and androgen deprivation therapy can provide new promising targets for treatment trials.

Association of Fascin and matrix metalloproteinase-9 expression with poor prognostic parameters in breast carcinoma of Egyptian women.

BACKGROUND: The effects of fascin on cell invasiveness involve changes in cell motility and matrix metalloproteinase-9 (MMP-9) activity. Previous studies on the prognostic value of fascin and MMP-9 in breast carcinoma revealed conflicting results. To date, no immunohistochemical studies have been performed to assess the possible association between them in breast carcinoma. This study is designed to correlate their expression with prognostic parameters in breast carcinoma and assess the relationship between them. METHODS: Immunohistochemical expression of fascin and MMP-9 was evaluated semi quantitatively in 67 cases of breast carcinoma regarding the percentage of positive cells. Chi square test and Fisher's exact test were used to examine the relationship between categorical variables. Kappa statistics was used to compute the measure of agreement between two investigational methods. RESULTS: Fascin and MMP-9 expressions were detected in 43.28% and 50.75% of breast carcinomas (respectively). Regarding the normal breast tissue, fascin expression was observed in myoepithelial cells and luminal cells of few ducts and acini. However, normal tissue showed negative MMP-9 expression. A significant relationship was observed between fascin and MMP-9 expression and lymph node metastases (p = 0.001 and 0.002 respectively), advanced tumor stage (p = 0.004 and 0.005 respectively), estrogen receptor negative (p = 0.002 and 0.005 respectively), progesterone receptor negative (p = 0.001 and 0.003 respectively) hormonal status and molecular subtypes (p = 0.0007 and 0.014 respectively). A significant strong agreement was detected between fascin and MMP-9 expression (p = 0.0001). More intense immunostaining of fascin and MMP-9 was observed at the invasive fronts compared with other areas of the tumor. Moreover, a significant moderate agreement between fascin and MMP-9 was found regarding the site of predominant intensity. CONCLUSION: Fascin and MMP-9 proteins are associated with parameters of poor prognosis in breast cancer. The significant strong agreement between the two markers supports the role of fascin in cell invasiveness by activating matrix proteases besides increasing cell motility. Both proteins may represent potential therapeutic targets for patients with breast cancer especially those with hormone receptor-negative status. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1421167695121127.

Comparative immunohistochemical assessment of cutaneous cyclooxygenase-2 enzyme expression in chronological aging and photoaging.

BACKGROUND/PURPOSE: Skin aging can be classified into chronological aging and photoaging. Cyclooxygenase-2 (COX-2) may be involved in ultraviolet-induced inflammation, photocarcinogenesis and the aging process. Studies done focused on assessing COX-2 expression after acute ultraviolet exposure and in photocarcinogenesis. Comparative assessment of COX-2 expression in chronological aging and photoaging was not previously studied. We aimed to compare COX-2 expression in chronological aging and photoaging. METHODS: Sixty participants were included (20 with chronological aging, 20 with photoaging, and 20 non-skin-aged contributors as controls). Fitzpatrick skin type and Glogau's photoaging type were assessed. Immunohistochemical evaluation of COX-2 was done in biopsies from sun-protected skin in the chronological aging and control groups, and from sun-exposed skin in the photoaging group. RESULTS: Comparison between each two groups showed a high statistically significant difference, with the highest percentage of mild, moderate and marked expression in the control, chronological aging and photoaging groups, respectively. A high statistically significant positive correlation was found between grading of solar elastosis in the photoaging group and COX-2 expression parameters. CONCLUSION: COX-2 expression is significantly higher in chronologically aged and photoaged skin than the normal young skin. This level of expression is significantly higher in photoaging than in chronological aging. COX-2 expression is positively related with the degree of solar elastosis in photoaging.