Renal lesions in von Hippel-Lindau disease: immunohistochemical expressionof nephron differentiation molecules, adhesion molecules and apoptosis proteins

Aims: Renal lesions in von Hippel-Lindau disease comprise clear cell simple cysts, atypical cysts and carcinomas. Although histological and molecular studies suggest that cystic lesions may represent precursors of carcinomas, there is no detailed phenotypic evidence of their relationship. Methods and results: To investigate such a possible relationship between cy stic lesions and solid carcinomas, we studied the pathological and immunohi stochemical features of 328 lesions of 33 kidneys originating from 23 patie nts with von Hippel-Lindau disease, using a panel of antibodies directed ag ainst cytoskeleton proteins, cell surface proteins, integrin subunits, adhe sion molecules, lectins, and apoptosis and proliferation markers. Solid car cinomas (n = 175) were all of clear cell type and mostly nuclear grade 1. C ystic lesions (n = 138) consisted of cystic clear cell carcinomas (n = 15), atypical cysts (n = 20) and simple cysts (n = 103). Clear cells of the sim ple cysts, atypical cysts and solid carcinomas coexpressed cytokeratins (CK 8, CK19) and vimentin, and expressed a similar pattern of tubular markers ( CD24, tetraglonolobus), integrin subunits (alpha 3, alpha 5, alpha 6, alpha v, beta 1) and cell adhesion molecules (ICAM 1, VCAM 1). In all lesions st udied, proliferation rate (MIB1 index) was low, and apoptosis marker expres sion (fragmented DNA, p53, bcl-2) inconspicuous. Conclusions: Phenotypic alterations found in solid renal cell carcinomas ar e already present in simple and atypical renal cysts of von Hippel-Lindau d isease.