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

Int J Cancer. 2000 Jul 20;89(4):350-5. doi: 10.1002/1097-0215(20000720)89:4<350::aid-ijc6>;2-3.


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, chi(2) = 28.1). We observed decreased p27 protein in higher pT categories (P < 0.001, chi(2) = 24.7) and in multiple tumor nodules (P < 0.001, chi(2) = 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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / surgery
  • Cell Cycle Proteins*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / surgery
  • Lymphatic Metastasis
  • Microtubule-Associated Proteins / biosynthesis*
  • Middle Aged
  • Neoplasm Staging
  • RNA, Messenger / biosynthesis
  • Retrospective Studies
  • Survival Analysis
  • Tumor Suppressor Proteins*


  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases