PROGRESSION OF HEPATOCELLULAR-CARCINOMA AS REFLECTED BY NUCLEAR-DNA PLOIDY AND CELLULAR-DIFFERENTIATION

Background/Aims: Intratumor heterogeneity of DNA ploidy within a singl e hepatocellular carcinoma is not well understood, The present study w as designed to examine the histologic distribution of intratumor DNA p loidy in hepatocellular carcinomas of different growth types in relati on to cell differentiation. Methods: Twenty patients (16 men and four women; mean age, 60.2 years) with hepatocellular carcinoma (mean diame ter, 4.3 cm) were studied, One hundred and twenty-seven samples from d ifferent sites of each tumor were analyzed by determination of the nuc lear DNA content and histological examination, Results: The DNA ploidy was heterogeneous in nine (45%) of the 20 tumors, Five tumors had a m ixture of diploid and aneuploid regions, and the remaining four consis ted of aneuploid regions with different DNA indices. There was no sign ificant difference in patient characteristics between the heterogeneou s and homogroups, A significant correlation was found between tumor gr owth type and the incidence of heterogeneity, Only 16% of single nodul ar carcinomas without intratumor septal formation exhibited heterogene ity, while single nodular tumors with septal formation or confluent mu ltinodular tumors were associated with high incidences of different DN A ploidy patterns or DNA indices, There was no aneuploidy in well-diff erentiated foci, while aneuploidy was frequently found in moderately o r poorly differentiated foci (incidences of 67% and 74%, respectively) , Conclusions: Heterogeneity of DNA ploidy may develop along with chan ges in growth pattern and cell dedifferentiation or by confluence of n odules originating from different tumor cell clones.