High-density allelotyping of chromosome 8p in hepatocellular carcinoma and clinicopathologic correlation.

Abstract

Allelic deletions are frequent genetic alterations in patients with hepatocellular carcinoma (HCC). To evaluate the allelic losses on chromosome 8p in HCC patients and define their clinicopathologic significance, we performed high-density allelotyping on 8p in 60 patients with HCC and analyzed the clinicopathologic correlation. Using 24 microsatellite markers, allelic losses on 8p were frequent. Loss of heterozygosity (LOH) at one or more loci was observed in 34 (57%) HCC patients. When the allelic losses were compared between groups categorized by clinicopathologic variables, significant correlation was found between tumors with interstitial losses and larger tumor size (> 5 cm; P = 0.026). In addition, allelic loss at D8S298 at 8p22 was associated closely with venous permeation, tumor microsatellite formation, and larger tumor size (P = 0.019, 0.024, and 0.007, respectively). LOH at locus D8S1721 at 8p23.1 was seen more frequently in nonencapsulated tumors (P = 0.007) and LOH at D8S1771 at 8p21.3 was associated with a larger tumor size and poorer cellular differentiation (P = 0.018 and 0.049, respectively). Allelic losses on 8p are frequent in HCC patients. Association of allelic losses at specific loci on 8p with a more aggressive tumor behavior suggests that loss/inactivation of putative tumor suppressor gene(s) located at these regions may confer a tumor growth advantage and contribute to the progression of HCC.