title: Renal lesions in von Hippel-Lindau disease: immunohistochemical expression of nephron differentiation molecules, adhesion molecules and apoptosis proteins.
abstract: OBJECTIVE
  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.
  
  
  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 (alpha3, alpha5, alpha6, alphav, beta1) 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.
authors.affiliation: Laboratoire de Pathologie Rénale; Service de Néphrologie, Hôptal Necker, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Paraf
authors.forename: D
authors.initials: D
authors.lastname: Chauveau
authors.forename: Y
authors.initials: Y
authors.lastname: Chrétien
authors.forename: S
authors.initials: S
authors.lastname: Richard
authors.forename: J P
authors.initials: JP
authors.lastname: Grünfeld
authors.forename: D
authors.initials: D
authors.lastname: Droz
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000737:chemistry / Q000473:pathology; D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000032:analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016023:Integrins / Q000032:analysis; D052177:Kidney Diseases, Cystic / Q000737:chemistry / Q000473:pathology; D007680:Kidney Neoplasms / Q000737:chemistry / Q000473:pathology*; D007684:Kidney Tubules / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D006623:von Hippel-Lindau Disease / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D016023:Integrins; D008565:Membrane Proteins; D009363:Neoplasm Proteins