Background The incidence of renal cell carcinoma (RCC), the most common malignant renal epithelial tumour, is increasing worldwide. Patients usually present with advanced disease and mostly have unpredicted clinical behaviour. A variety of prognostic factors have been proposed as useful parameters, however many of them showed limited clinical value. Thus, the discovery of novel prognostic markers, which might help in predicting patients' outcome and additional new targets to treat this disease are still in great demand. EphA2, a receptor tyrosine kinase, was found to be overexpressed in several malignancies and its expression in different tumours was found to be associated with poor prognostic features. In addition, a group of emerging strategies was recently introduced to target this receptor and found to show anti‐tumorigenic activity in various pre‐clinical cancer models. Aim To investigate the prognostic value of EphA2 expression in RCC patients and its association with other clinicopathological parameters as well as Ki67 expression, which is a well‐known proliferative and prognostic marker. Materials and Methods The expression of EphA2 and Ki67 was investigated immunohistochemically, and the results were correlated with the different clinicopathological parameters in 50 primary tumour blocks obtained from RCC cases surgically managed in the Urology Department, Alexandria University Main Hospital, during the period (2012–2015). In addition, the association between the EphA2 mRNA expression and the tumour stage as well as the patient outcome was also evaluated using two large publicly available databases. Results Our results showed a significant association between EphA2 expression and the tumour size, the nuclear grade, the tumour stage, the patient's outcome and the Ki‐67 expression (P < 0.05 for all). The same trend was also observed with EphA2 mRNA expression using larger patients' cohorts in two publicly available databases. Notably, EphA2 protein expression showed higher levels of co‐expression with the proliferative marker Ki67. Conclusion We concluded that higher expression of EphA2 and Ki67 in tumour tissues predicts a locally aggressive behaviour and poor outcome of RCC patients. Moreover, our results give a rationale for the potential benefits of using novel therapeutic strategies with the aim of targeting EphA2 receptor in RCC that might help in improving their outcome. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
BackgroundThe incidence of renal cell carcinoma (RCC), the most common malignant renal epithelial tumour, is increasing worldwide. Patients usually present with advanced disease and mostly have unpredicted clinical behaviour. A variety of prognostic factors have been proposed as useful parameters, however many of them showed limited clinical value. Thus, the discovery of novel prognostic markers, which might help in predicting patients' outcome and additional new targets to treat this disease are still in great demand. EphA2, a receptor tyrosine kinase, was found to be overexpressed in several malignancies and its expression in different tumours was found to be associated with poor prognostic features. In addition, a group of emerging strategies was recently introduced to target this receptor and found to show anti‐tumorigenic activity in various pre‐clinical cancer models.AimTo investigate the prognostic value of EphA2 expression in RCC patients and its association with other clinicopathological parameters as well as Ki67 expression, which is a well‐known proliferative and prognostic marker.Materials and MethodsThe expression of EphA2 and Ki67 was investigated immunohistochemically, and the results were correlated with the different clinicopathological parameters in 50 primary tumour blocks obtained from RCC cases surgically managed in the Urology Department, Alexandria University Main Hospital, during the period (2012–2015). In addition, the association between the EphA2 mRNA expression and the tumour stage as well as the patient outcome was also evaluated using two large publicly available databases.ResultsOur results showed a significant association between EphA2 expression and the tumour size, the nuclear grade, the tumour stage, the patient's outcome and the Ki‐67 expression (P < 0.05 for all). The same trend was also observed with EphA2 mRNA expression using larger patients' cohorts in two publicly available databases. Notably, EphA2 protein expression showed higher levels of co‐expression with the proliferative marker Ki67.ConclusionWe concluded that higher expression of EphA2 and Ki67 in tumour tissues predicts a locally aggressive behaviour and poor outcome of RCC patients. Moreover, our results give a rationale for the potential benefits of using novel therapeutic strategies with the aim of targeting EphA2 receptor in RCC that might help in improving their outcome.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Background: Diffuse large B cell lymphoma (DLBCL) is considered the most common type of non-Hodgkin lymphoma. The global incidence of DLBCL has been doubled in the past decades, highlighting the need for more effective treatment regimens. The curability of DLBCL is heavily influenced by a number of factors, such as the age, the international prognostic index (IPI) score, the molecular cell of origin (COO) subtype, and presence/ absence of specific chromosomal rearrangements or protein expression. Recent gene profiling studies have classified DLBCL into two main categories, germinal center B-cell type (GCB) and activated B-cell type (ABC). Validation of these subtypes has become more applicable after the immunohistochemical algorithm suggested by Hans, which included three commercially available markers, CD10, BCL6, and MUM-1/IRF4. In addition to this classification, DLBCL prognostic models based on different sets of genes or immunohistochemical markers have been proposed. More recently, DLBCLs with translocations of MYC, along with a B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangement, are now called double-hit lymphoma (DHL) or triple-hit lymphoma (THL), respectively. Furthermore, the co-expre sion of MYC and BCL2 proteins without underlying rearrangements is considered a new adverse prognostic indicator termed double-expressor lymphoma (DEL). The present study is aiming to combine morphological, immunophenotypical, and genetic features of DLBCLs to reach a more reproducible subtyping. Aim: To identify the relation between clinicopathological features as patient age, sex, site of tumor, clinical presentation and tumor stage and the germinal center differentiation in DLBCL (germinal center B-cell (GCB) or activated B-cell (ABC)) and the double/triple genetic hits status.Material and Methods: The material of this study comprised 52 formalin-fixed paraffin- embedded blocks representative of diffuse large B cell lymphoma cases retrieved from the archival material available at the Pathology Department, Faculty of Medicine, Alexandria University. Subclassification of cases into (germinal center / and post-germinal center types) using a panel of immunohistochemical markers including CD10, BCL6 and MUM1 was done and scoring of double/triple hit expression using a panel of immunohistochemical markers including c-MYC, BCL6 and BCL2 was also done and correlation with their subtypes and clinical data was performed.Results: there was significant association between germinal center differentiation and tumor stage (MCp= 0.018).Conclusion: Germinal center differentiation status is a valid method to evaluate the prognosis of DLBCL.
Renal cell carcinoma (RCC) is one of the most common renal malignancies. Reliable validated biomarkers are essential for optimum disease diagnosis and prognosis. Copines are a family of calcium‐dependent phospholipid‐binding proteins. Copines 1 and 3 are members of the copine family, and their expression is reported to be associated with various cancers. The aims of this observational study are to investigate the prognostic value of Copines 1 and 3 in RCC patients, and their association with demographic and clinicopathological parameters. Copine 1 and 3 immunohistochemical (IHC) staining was performed on whole sections representative of 50 patients with RCC. Bioinformatics analysis was also performed using publicly available databases. The results revealed a significant association between Copine 1 expression and patient's age, nuclear grade, tumour stage, EphA2 and Ki‐67 expression. Bioinformatics analysis showed a similar trend with Copine 1 mRNA expression. Interestingly, the results revealed a positive association between Copine 1 and EphA2, Ki67 expressions. There was no significant association between Copine 3 expression and any demographic or clinicopathological parameters. In conclusion, this study supports potential use of Copine 1 as an independent biomarker or in combination with both EphA2 and Ki‐67 for better‐personalized medicine to improve the disease outcome.
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