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

Andrea Tannapfel*, Dorothee Grund, Alexander Katalinic, Dirk Uhlmann, Ferdinand Köckerling, Ulrike Haugwitz, Mark Wasner, Johann Hauss, Kurt Engeland, Christian Wittekind

*Corresponding author for this work
81 Citations (Scopus)


Reduced expression of the cyclin-dependent kinase inhibitor p27 has previously been correlated with fatal clinical outcome in some tumors, including gastric, breast, and prostate cancers. For hepatocellular carcinoma, the findings are equivocal. In situ hybridization and immunohistochemistry were performed on a series of 203 curatively (R0) resected hepatocellular carcinomas 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 significance, and finally patient survival. Whereas p27 mRNA was expressed homogeneously in all carcinomas examined, the p27 protein was found in various amounts. The labeling index of p27 protein was significantly lower in advanced stages of the disease (P < 0.001, χ2 = 28.1). We observed decreased p27 protein in higher pT categories (P < 0.001, χ2 = 24.7) and in multiple tumor nodules (P < 0.001, χ2 = 9.3). Multivariate Cox survival analysis identified age, co-existing cirrhosis, and Edmondson grade as independent prognostic factors. We conclude that evaluation of p27 in hepatocellular carcinoma is useful to predict stage of disease and may have clinical significance, e.g., in predicting optimal therapeutic regimes. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
JournalInternational Journal of Cancer
Issue number4
Pages (from-to)350-355
Number of pages6
Publication statusPublished - 20.07.2000


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