Expression of mutant nuclear beta-catenin correlates with non-invasive hepatocellular carcinoma, absence of portal vein spread, and good prognosis

beta -catenin has functions both in the cadherin-mediated cell adhesion sys tem and in the signalling pathway that mediates dorsal axis patterning in t he embryo; it has been shown to be aberrantly expressed or mutated in diver se types of human tumour, but the biological significance of this remains t o be clarified. To elucidate the clinical implications of aberrant beta -ca tenin expression and the potential differences between mutant and wild-type beta -catenin protein expression in hepatocellular carcinoma (HCC), the pr otein expression was analysed by immunohistochemical staining, supplemented by the analysis of gene mutation. Among 372 unifocal primary HCCs, beta -c atenin was detected in the tumour cell membrane alone in 272 tumours (group A) and also in the nuclei in 100 (group B), In group A, 148 tumours had de creased beta -catenin expression, but the reduction did not correlate with invasion or prognosis. When compared with group A, however, group B had sig nificantly lower frequencies of hepatitis B surface antigen carrier (p = 0. 015), and alpha -fetoprotein elevation (p = 0.0003), but more often had non -invasive HCC (p < 0.001) and better survival (p = 0.01). Nuclear <beta>-ca tenin expression strongly correlated with mutation of the gene (p < 0.00001 ). In group B, HCC with mutant nuclear <beta>-catenin correlated positively with non-invasive (stage 1) tumour and inversely with portal vein tumour t hrombi (stage 3 HCC), and had significantly better 5-year survival,p < 0.00 1 and p < 0.0003, respectively, These results suggest that beta -catenin mu tation plays an important role in the tumourigenesis of a subset of HCC of good prognosis, and that mutant and mild-type nuclear beta -catenin protein s are not functionally equivalent. Copyright (C) 2000 John Wiley & Sons, Lt d.