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

Background: Allelic deletions are frequent genetic alterations in patients with hepatocellular carcinoma (HCC).

Methods: 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.

Results: 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).

Conclusions: 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.