Diverse p53 gene aberration in hepatocellular carcinoma detected by dual-color fluorescence in situ hybridization.

Abstract

In order to evaluate loss of the p53 gene more precisely, we performed dual-color fluorescence in situ hybridization (dual-color FISH) for chromosome 17 and p53 gene together with DNA polymorphism analysis of the p53 gene in hepatocellular carcinoma (HCC). Dual-color FISH using probes specific for the centromere of chromosome 17 and the p53 gene was performed for 41 HCC and DNA polymorphism analysis was also performed for them. Of the 34 HCC tested by dual-color FISH, 20 had loss of at least one p53 gene (58.8%). In contrast, of the 32 HCC tested by DNA polymorphism analysis, 23 gave informative results, among which only eight had loss of heterozygosity (LOH) of the p53 gene (34.8%). Notably, among 14 cases positive for loss of the p53 gene by dual-color FISH, seven cases were negative for LOH of the p53 gene. Moreover, dual-color FISH revealed that the percentage of cells that lost at least one p53 gene increased as the HCC became less differentiated (P < 0.01), whereas LOH did not reveal any such correlation. These data suggest that loss of the p53 gene was present in a considerable number of HCC, and diversity of the p53 gene aberration increases with progression of HCC. Dual-color FISH is an effective method for detection of p53 gene aberration, and it can provide new insight into oncogenesis in HCC.