Expression of HGF/SF and Met protein is associated with genetic alterations of VHL gene in primary renal cell carcinomas.
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.
Oh
Ro Ra
RR
Department of Pathology and Genetic Oncology Laboratory, College of Medicine, The Catholic University of Korea, Seoul.
Park
Jik Young
JY
Lee
Jong Heun
JH
Shin
Min Sun
MS
Kim
Hong Sug
HS
Lee
Sang Kyu
SK
Kim
Young Sil
YS
Lee
Sug Hyung
SH
Lee
Sie Nae
SN
Yang
Young Mok
YM
Yoo
Nam Jin
NJ
Lee
Jung Young
JY
Park
Won Sang
WS
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
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