The roles of loss of heterozygosity at 8p22 in the molecular classification of patients with hepatocellular carcinoma, with special reference to survival after surgical operation

B54

Purpose:Our previous studies have demonstrated that chromosome 8p deletion, particularly 8p11-12 and 8p21-23, correlates with metastasis of human hepatocellular carcinoma (HCC). The purpose of this study was to determine whether allelic losses on these regions including 8p could be used in predicting the prognosis of patients with HCC.Experimental Design: A total of 208 patients with TNM stage I or II of HCC who underwent curative liver resection from January 1999 to March 2000 were enrolled. Genomic DNA was extracted from microdissected HCC tissues. LOH was examined using 10 microsatellite markers located at the regions of chromosome 8p mentioned above, and its association with 5-year overall survival (OS) and disease-free survival (DFS) of patients was analyzed.Results: The mean heterozygosity of these loci was 69.8%. The LOH frequencies assessed from informative cases at the loci tested were also high, with a range from 32.6% (D8S1721) to 48.8% (D8S261), and the three most frequently altered loci were D8S261(8p22). In univariate analyses, LOH on D8S29857 (8p22) (39.6%) was associated with a worse 5-year OS (P=0.037) and DFS (P<0.001) of the entire cohort of patients. And more, even in those patients with TNM stage I of HCC, LOH D8S298 were also found to be associated with decreases in both OS (P=0.008) and DFS (P=0.038). In a multivariate model, D8S298 LOH was one of the independent predictors for decreased DFS (P=0.019) and decreased OS (P=0.014).Conclusion: LOH at D8S298 is independently associated with a worse survival in stage I and II patients with curative resection for HCC.v:textbox>v:textbox>