Analysis of clonality in hepatocellular carcinoma

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Analysis of X-chromosome inactivation patterns in females has been used to assess the clonality of various tumors. We analyzed 27 female liver tumors, including 18 samples obtained by ultrasonically guided thin-needle biopsies. By analysis of the heterogeneity of phosphoglycerate kinase(PGK)gene using conventional Southern blot hybridization and/or polymerase chain rection, 11/27 (41%) cases were found to be heterozygous at the gene. Of these informative 11 cases with liver tumors, 7 cases were "large" tumors (>25mm in diameter) and 4 cases were "small" tumors (>25mm in diameter). All the 7 "large" tumors showed monoclonal patterns by the PGK gene analysis. Of the 4 "small" tumors, two showed monoclonal and the other two showed polyclonal patterns. The two with monoclonal patterns were pathologically diagnosed as hepatocellular carcinoma despite their small sizes (20mm and 23mm). Of the two with polyclonal patterns, the smallest one (15mm) was diagnosed as benign adenomatous hyperplasia, and the other as hepatocellular carcinoma heavily infiltrated by lymphocytes. Our study has demonstrated that this method enables us to analyze the clonality of small materials like biopsy specimens and it may be helpful in certain cases in which the pathological findings are ambiguous.