Allelic imbalance on 16q in small, unifocal hepatocellular carcinoma - Correlation with HBV and HCV infections and cellular proliferation rate

In advanced hepatocellular carcinoma (HCC), allelic loss on chromosome 16q may occur. To better define the frequency of this alteration in small HCC a nd to more closely identify the affected region for further positional clon ing of the putative tumor suppressor gene contained in this region, microsa tellite polymorphism analysis was conducted on small, unifocal HCC, without signs of intrahepatic or systemic spread. We also tried to assess its poss ible correlation with hepatitis virus infections (HBV and HCV) and cellular proliferation rate. DNA from 35 small (<4 cm), unifocal HCC and from the c orresponding nontumorous surrounding tissue was analyzed by 10 sets of micr osatellite polymorphic markers. Serologic markers for hepatitis virus B and C infections were investigated in all cases. AgNOR protein quantity was as sessed by image analysis on cryostatic sections stained with silver. The pe rcentage of tumours with allelic imbalance ranged from 11.1 to 37%. The min imal involved region was assessed at 16q24.3, corresponding to the D16S413 marker, which was also the most commonly affected locus (10 of 27 informati ve cases, 37%). Allelic imbalance on chromosome 16q was significantly assoc iated with HBV infection: 8 of 10 cases showed an actual or previous HBV in fection in the group showing allelic imbalance, versus 6 with a previous HB V infection out of 25 in the control group (P < 0.01). No difference was fo und as Ear as HCV infection is concerned. The mean (+/-SE) AgNOR protein va lue in six cases showing allelic imbalance was 8.36 +/- 1.2 mu m(2), compar ed to 6.45 +/- 0.68 mu m(2) in 13 cases retaining both the alleles at 16q b ut the difference proved not statistically significant. In conclusion, in t his series of small, unifocal HCC the minimal region of allelic imbalance o n 16q was restricted to 16q24.3. It was found to be associated with HBV inf ection but not with increased cellular proliferation rate.