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

• Published in: Histopathology 2000-05, Vol.36 (5), p.457-465
• Main Authors: PARAF, F, CHAUVEAU, D, CHRETIEN, Y, RICHARD, S, GRÜNFELD, J.-P, DROZ, D
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Clear Cell - chemistry; Adenocarcinoma, Clear Cell - pathology; adhesion molecules; Adolescent; Adult; Apoptosis; Biological and medical sciences; Biomarkers, Tumor - analysis; Carcinoma, Renal Cell - chemistry; Carcinoma, Renal Cell - pathology; Cell Adhesion Molecules - analysis; Cytoskeletal Proteins - analysis; DNA, Neoplasm - analysis; Female; Humans; Immunoenzyme Techniques; immunohistochemistry; Integrins - analysis; Kidney Diseases, Cystic - chemistry; Kidney Diseases, Cystic - pathology; Kidney Neoplasms - chemistry; Kidney Neoplasms - pathology; Kidney Tubules - chemistry; Kidney Tubules - pathology; Kidneys; Male; Medical sciences; Membrane Proteins - analysis; Middle Aged; Neoplasm Proteins - analysis; Nephrology. Urinary tract diseases; renal cell carcinoma; renal cysts; renal tubular markers; Tumors of the urinary system; von Hippel-Lindau disease; von Hippel-Lindau Disease - pathology
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1046/j.1365-2559.2000.00857.x

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 cystic lesions and solid carcinomas, we studied the pathological and immunohistochemical features of 328 lesions of 33 kidneys originating from 23 patients with von Hippel–Lindau disease, using a panel of antibodies directed against cytoskeleton proteins, cell surface proteins, integrin subunits, adhesion molecules, lectins, and apoptosis and proliferation markers. Solid carcinomas (n = 175) were all of clear cell type and mostly nuclear grade 1. Cystic lesions (n = 138) consisted of cystic clear cell carcinomas (n = 15), atypical cysts (n = 20) and simple cysts (n = 103). Clear cells of the simple cysts, atypical cysts and solid carcinomas coexpressed cytokeratins (CK8, CK19) and vimentin, and expressed a similar pattern of tubular markers (CD24, tetraglonolobus), integrin subunits (α3, α5, α6, αv, β1) and cell adhesion molecules (ICAM 1, VCAM 1). In all lesions studied, proliferation rate (MIB1 index) was low, and apoptosis marker expression (fragmented DNA, p53, bcl‐2) inconspicuous. Conclusions Phenotypic alterations found in solid renal cell carcinomas are already present in simple and atypical renal cysts of von Hippel–Lindau disease.