Decreased expression of p27 protein is associated with advanced tumor stage in hepatocellular carcinoma

Reduced expression of the cyclin-dependent kinase inhibitor p27 has previou sly been correlated with fatal clinical outcome in some tumors, including g astric, breast, and prostate cancers. For hepatocellular carcinoma, the fin dings are equivocal. In situ hybridization and immunohistochemistry were pe rformed an a series of 203 curatively (R0) resected hepatocellular carcinom as and in corresponding non-cancerous liver tissue to detect p27. Patients receiving liver transplantation were excluded. The results were correlated with histopathological stage according to the UICC system, Edmondson grade, several other histopathological factors of possible prognostic significanc e, and finally patient survival. Whereas p27 mRNA was expressed homogeneous ly in all carcinomas examined, the p27 protein was found in various amounts . The labeling index of p27 protein was significantly tower in advanced sta ges of the disease (P < 0.001, chi(2) = 28.1). We observed decreased p27 pr otein in higher pT categories (P < 0.001, chi(2) = 24.7) and in multiple tu mor nodules (P < 0.001, chi(2) = 9.3). Multivariate Cox survival analysis i dentified age, co-existing cirrhosis, and Edmondson grade as independent pr ognostic factors. We conclude that evaluation of p27 in hepatocellular carc inoma is useful to predict stage of disease and may have clinical significa nce, e.g, in predicting optimal therapeutic regimes. (C) 2000 Wiley-Liss, I nc.