Prognostic Impact of Multiple Allelic Losses on Metastatic Recurrence in Hepatocellular Carcinoma after Curative Resection

Abstract

Loss of heterozygosity (LOH) on chromosomes 13q, 16q and 17p has been associated with the progression of hepatocellular carcinoma (HCC). To investigate the prognostic impact of such LOH, we examined the metastasis-free survival of curatively resected HCC cases, in whom these LOHs were analyzed. Among the 49 HCC patients examined, the frequency of LOHs was 28% on 13q, 33% on 16q and 40% on 17p. The patients were followed up for metastatic recurrence after surgery and for analysis of the relationship between chromosomal changes and patients' metastasis-free survival. Univariate survival analysis showed the presence of LOH on 16q, 17p and the number of chromosomes with LOH were significantly and negatively associated with metastasis-free survival, indicating that patients with LOH on multiple chromosomes had a poorer prognosis after surgery than those with LOH on a single chromosome or no LOH. Multivariate Cox survival analysis identified the presence of LOH on 16q and the number of chromosomes with LOH as the most significant independent negatively predictive factors for metastasis-free survival. These findings indicate that accumulation of chromosomal changes is associated with metastatic behavior, and that LOH on 16q was the most useful prognostic indicator for metastasis after curative resection of HCC.