The prognostic value of ephrin type-A2 receptor and Ki-67 in renal cell carcinoma patients

Abstract

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.

Clinical significance of circulating tumour cells and Ki-67 in renal cell carcinoma

“…Ki-67, a nuclear protein that is associated with ribosomal RNA synthesis and may be necessary for proliferating cells, contributes to the enhanced proliferative activity of intrinsic cell populations in malignant tumours [ 14 ]. Therefore, Ki-67 has been considered a biomarker of RCC that could be used in routine clinical practice [ 11 , 12 , 15 , 16 ]. In view of its clinical significance, Ki-67 has been widely used as a diagnostic approach for assessing tumour malignancies [ 17 , 18 ].…”

Exploring vasculogenesis in the normal human kidney and clear cell renal cell carcinoma: insights from development to tumor progression and biomarkers for therapy response

“…In their study, Talaat et al. ( 123 ) emphasized that patients with RCC are prone to displaying a locally aggressive behavior and an unfavorable prognosis when their tumor tissues demonstrate elevated levels of EphA2 and Ki-67. In addition, these results support the idea that people with RCC may benefit from new treatment methods that focus on the EphA2 receptor to improve their prognosis.…”

Clinical Significance of Circulating Tumor Cells and Ki-67 in Renal Cell Carcinoma

“…14 Therefore, Ki-67 has been considered as a biomarker of RCC which could be used in routine clinical practice. 11,12,15,16 In view of its clinical signi cance, the Ki67 has been widely applied as a diagnostic approach for assessing a number of human malignancies. 17,18 The aim of the present study was to detect the changes of CTC and CTM counts and positive rate in peripheral blood of patients with RCC during perioperative period, and to explore their correlation with clinical and pathological features.…”