Subcellular localization and protein levels of cyclin-dependent kinase inhibitor p27 independently predict for survival in epithelial ovarian cancer

Clin Cancer Res. 2005 Dec 1;11(23):8384-90. doi: 10.1158/1078-0432.CCR-05-1270.

Abstract

Purpose: p27 protein is regarded as a valuable prognostic biomarker in cancer with a potential use as a molecular target. However, different methods of immunohistochemical assessment have yielded conflicting results. Here, we sought to determine the prognostic value of p27 in ovarian cancer using a novel method of compartmentalized in situ protein analysis.

Experimental design: A tissue array composed of 150 advanced stage ovarian cancers uniformly treated, with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of p27 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis [automated quantitative analysis (AQUA)].

Results: The mean follow-up time of the patients was 34.3 months. Patients with low Fédération Internationale des Gynaecologistes et Obstetristes stage were more likely to have low nuclear p27 expression (P = 0.008). Low nuclear p27 expression was associated with improved 3-year overall survival (66% versus 20%, P = 0.0047) and disease-free survival (27% versus 12%, P = 0.022). In multivariable analysis, adjusting for well-characterized prognostic variables, low nuclear p27 expression level was the most significant prognostic factor for both disease-free and overall survival.

Conclusions: Our results indicate that quantitative assessment of nuclear p27 expression level by automated in situ quantitative analysis is a strong predictor for outcome in ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cell Differentiation
  • Cohort Studies
  • Combined Modality Therapy
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / mortality
  • Cystadenocarcinoma, Serous / therapy
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / therapy
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality*
  • Ovarian Neoplasms / therapy
  • Prognosis
  • Subcellular Fractions
  • Survival Rate
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p27