title: Expression of HGF/SF and Met protein is associated with genetic alterations of VHL gene in primary renal cell carcinomas.
abstract: We analyzed the genetic alterations of VHL, HGF/SF, and Met genes and the expression pattern of HGF/SF and Met protein in 26 renal cell carcinomas (RCCs). We found five mutations of the VHL gene and frequent LOH (50%) only in non-papillary clear cell RCC. We found six cases in which the CpG island of VHL was methylated. In addition, one missense mutation of the HGF/SF gene was detected in clear cell RCC. HGF/SF and Met protein were expressed in 84.6% and 80.7% of RCCs, respectively. All of the cases with the genetic alterations of VHL or HGF/SF demonstrated strong expression of HGF/SF and Met protein in RCC cells. Statistically, genetic alterations of VHL and HGF/SF were significantly correlated with HGF/SF and Met expression (Fisher's exact test, p=0.022 and p=0.0070). Thus, these results strongly suggest that the expression of HGF/SF and Met protein is closely associated with the genetic alterations of VHL and HGF/SF in primary RCCs.
authors.affiliation: Department of Pathology and Genetic Oncology Laboratory, College of Medicine, The Catholic University of Korea, Seoul.
authors.forename: Ro Ra
authors.initials: RR
authors.lastname: Oh
authors.forename: Jik Young
authors.initials: JY
authors.lastname: Park
authors.forename: Jong Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Shin
authors.forename: Hong Sug
authors.initials: HS
authors.lastname: Kim
authors.forename: Sang Kyu
authors.initials: SK
authors.lastname: Lee
authors.forename: Young Sil
authors.initials: YS
authors.lastname: Kim
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Sie Nae
authors.initials: SN
authors.lastname: Lee
authors.forename: Young Mok
authors.initials: YM
authors.lastname: Yang
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D005260:Female; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D008025:Ligases / Q000235:genetics*; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
chemical_list: D025521:Tumor Suppressor Proteins; D017228:Hepatocyte Growth Factor; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D019859:Proto-Oncogene Proteins c-met; D008025:Ligases; C497446:VHL protein, human