Loss of p27Kip1 expression independently predicts poor prognosis for patients with resectable pancreatic adenocarcinoma

Cancer. 1999 Mar 15;85(6):1250-60.

Abstract

Background: As a universal inhibitor of cyclin-dependent kinases in mammalian cells, p27Kip1 expression has been implicated in tumor progression and has proved to be a prognostic predictor for several human cancers. In this study, the authors investigated the expression of p27Kip1 and its potential prognostic significance in patients with resectable pancreatic adenocarcinoma.

Methods: The correlation between p27Kip1 expression and prognosis was investigated retrospectively in 38 patients who had undergone resection of pancreatic adenocarcinoma including 2 cystadenocarcinomas and 4 mucin-producing tumors. Immunohistochemical staining using an anti-p27Kip1 antibody, along with an assessment of tumor cell Ki-67 labeling index, was performed on resected specimens.

Results: p27Kip1 expression in pancreatic adenocarcinoma was decreased dramatically when compared with that in normal pancreatic tissue. Based on 35 cases available for survival analysis, loss of p27Kip1 expression in 16 cases defined as having no or <1% p27Kip1 positive tumor cells showed 1-, 1.5-, and 2-year survival rates of 37.5%, 15.6%, and 0%, respectively, in comparison with 1-, 2-, and 3-year survival rates of 68.4%, 62.2%, and 49.8%, respectively, in the other cases (P = 0.001). After excluding cases of cystadenocarcinoma and mucin-producing tumors, the survival advantage for patients with p27Kip1 positive tumors remained apparent (P = 0.024). In each Cox regression model, both those including cystadenocarcinoma and mucin-producing tumors and those that did not, p27Kip1 expression proved to be an independent predictor for overall survival by multivariate analysis.

Conclusions: These results reveal the significance of p27Kip1 immunostaining in predicting the outcome of patients with resectable pancreatic adenocarcinoma, adding a novel predictor in the evaluation of prognosis for this lethal disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemistry*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Cell Cycle Proteins*
  • Cell Division
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Male
  • Microtubule-Associated Proteins / analysis*
  • Middle Aged
  • Multivariate Analysis
  • Pancreas / chemistry
  • Pancreatic Neoplasms / chemistry*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Tumor Suppressor Proteins*

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Ki-67 Antigen
  • Microtubule-Associated Proteins
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases