LOSS OF E-CADHERINS AND N-CADHERINS IN AD VANCED RENAL-CELL

Homotypic contact of normal epithelial cells is mediated by calcium-de pendent cell adhesion molecules detected in intercellular adherens jun ctions, the cadherins. Loss of E-cadherin has been found to be an impo rtant prognostic factor in cancers of bladder or prostate. Few data ar e available on the role of cadherins in normal kidney and RCC. It was therefore the purpose of our study to examine expression of E- and N-c adherins in normal kidney and RCC. Specimens of normal kidney and RCC from 42 patients were examined for expression of E- and N-cadherins by immunohistochemistry using monoclonal antibodies. A sensitive method employing a gold labelled second antibody with subsequent silver enhan cement was used for detection of antibody binding. All patients (n = 4 2) had strong expression of N-cadherin in specimens of normal kidney, whereas E-cadherin was expressed in 4/42, weakly expressed in 21/42 pa tients and undetecable in 17/42 normal kidneys. The strong staining fo r N-cadherin observed in normal kidney was lost in the corresponding t umors in 30/42 (71 %) patients. 12 patients had strong staining for N- cadherin in their tumors. Except for one patient, none of these patien ts had N+, M(+) or G3 disease. Among the patients with loss of N cadhe rin expression there were 5 patients with nodal metastasis, 4 with dis tant metastasis and 9 with G3 tumors. From our data we conclude that N -cadherin ist the predominant homotypic cadherin-type adhesion molecul e in normal kidney. Loss of homotypic adhesion molecules Nand E-cadher in correlates with advanced disease. Therefore, expression of calcium- dependent homotypic adhesion molecules may provide additional prognost ic information in RCC.