Cadherins and integrins in renal cell carcinoma an immunohistochemical study

Abstract

Aims and background: The aim of this study was to determine the expression of cadherins and integrins in renal cell carcinoma (RCC) and their relationship with tumor morphology and TNM status. Methods: Cadherin and integrin expression was investigated using an indirect immunoperoxidase technique, applying antibodies to E-, N-, P- and VE-cadherin and to α1, α2, α3, α4, α5, α6, and αv integrin subunits. Correlation of semiquantitatively scored adhesion molecule levels with histopathological parameters (cytology, growth pattern, nuclear grade) and TNM status was performed for 24 RCCs (17 clear cell, 3 granular, 3 spindle cell and 1 chromophobe cell type according to the WHO classification). Results: E-cadherin and N-cadherin were present in most cases (88% and 67%, respectively) and were usually coexpressed. T3 RCCs displayed higher E-cadherin and N-cadherin levels than T1/T2 tumors regardless of tumor grade, suggesting that impairment of their function might exist without actual loss from tumor cells. P-cadherin was found focally in two RCCs only, while VE-cadherin was present on stromal vessel endothelium in five tumors, showing no differences with regard to cell type, growth pattern, tumor grade or TNM status. All integrins were present in the studied RCCs (ranging from 12% for α5 to 79% for α3), including those that are normally absent from adult kidney tissue (α4 and α5). Tumors of higher grade showed increased αv and decreased α6 levels, while RCCs with metastases less often showed diffuse α3 presence and never expressed α5 integrin. Conclusions: Our results suggest that the level of expression of N-cadherin and some integrins (most notably α3, α6 and α5) is associated with the capacity of RCC for local and distant spread, regardless of tumor grade.