Expression of cell cycle regulators p57(KIP2), cyclin D1, and cyclin E in epithelial ovarian tumors and survival

Hum Pathol. 2001 Aug;32(8):808-13. doi: 10.1053/hupa.2001.26462.


The search for new prognostic indicators is especially important in the diagnosis and treatment of ovarian cancer because clinicopathologic criteria currently used to predict survival are largely inadequate. We examined 2 groups of patients with epithelial ovarian cancer, 1 group of long-term survivors (>5 years), and 1 group of short-term survivors (<2 years) for levels of expression of the cell cycle regulators p57(KIP2), cyclin D1, and cyclin E and their relationship with survival. Our findings show that p57(KIP2) is not associated with prognosis, in contrast to p27(KIP1) expression, which is previously shown to be positively associated with long-term survival in univariate analysis (P =.001). Cyclin E expression, in contrast to cyclin D1 expression, is marginally associated with short-term survival in univariate analysis for a group of 53 women. Among the short-term survivors, 15 (65%) of 23 were positive for cyclin E expression, compared with only 11 (37%) of 30 long-term survivors (P = 0.054). This association remained significant (P =.04) in a logistic regression analysis adjusted simultaneously for performance status and extent of residual disease, the 2 strongest predictors of survival in our study. We also found a significant difference in the frequency of the cyclin E staining pattern between nonserous and serous ovarian tumor subtypes (P =.0002). Immunostaining for levels of cyclin E and p27(KIP1) expression may have potential as prognostic markers in the management of ovarian cancer.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Biomarkers, Tumor / metabolism
  • Cyclin D1 / metabolism*
  • Cyclin E / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p57
  • Disease-Free Survival
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Nuclear Proteins / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Retrospective Studies
  • Survival Rate


  • Biomarkers, Tumor
  • CDKN1C protein, human
  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p57
  • Nuclear Proteins
  • Cyclin D1