Tetrasomy 6 and 6q14 deletion are associated with better survival in hepatocellular carcinomas: a fluorescence in situ hybridization study of 77 cases

Abstract

We previously described frequent 6q14 deletion and polysomy 6 in 25 hepatocellular carcinomas (HCC) by fluorescence in situ hybridization (FISH). A more favorable prognosis was noted in patients with 6q14 deletions. To confirm this clinical association, a two-colored FISH study was carried out on 77 HCC using a combination of a yeast artificial chromosome probe (813_E_12) of the 6q14 region and a chromosome 6 centromeric probe (D6Z1) for simultaneous evaluation of the copy number change and chromosome arm deletion. The 77 HCC were divided into four groups according to the copy number of the centromeric signal: 26 with HCC (33.7%) were disomy for chromosome 6, 9 with HCC (11.7%) were trisomy, 29 with HCC (37.6%) were tetrasomy, and 13 with HCC (17%) were classified as hypersomy with presence of one major clone (>7%) of pentasomy or hexasomy of chromosome 6. Allelic loss at 6q14 was found in 40 with HCC (52%). The distribution of sex, age, stage, tumor size, tumor grade, and viral markers in each group showed no significant differences. An association with cirrhosis, however, was significantly lower in the hypersomy group ( P = 0.001). The tetrasomy group had the best survival. An interaction between 6q14 deletion and numerical change of chromosome 6 on patients' survival were also noted. For patients with 6q14 deletion, both disomy and tetrasomy groups had significantly better survival rates than trisomy and hypersomy groups. In contrast, no differences in survival rates could be observed among these four groups for patients without the 6q14 deletion. The association with more favorable prognosis shown in this study indicates that tetrasomy 6 and 6q14 deletion may play an important role in the tumorigenesis of hepatocellular carcinoma and is worthy of further investigation.