Expression and prognostic value of the cell-cycle regulatory proteins, Rb, p16MTS1, p21WAF1, p27KIP1, cyclin E, and cyclin D2, in ovarian cancer

Int J Gynecol Pathol. 2003 Apr;22(2):168-74. doi: 10.1097/00004347-200304000-00009.


To investigate the role of cell-cycle regulatory proteins in ovarian cancer, we performed immunohistochemistry for the cell-cycle promoters cyclin E and cyclin D2 and the cell-cycle inhibitors, Rb, p16MTS1, p21WAF1, and p27 KIP1, in 93 ovarian carcinomas (77 with follow-up data). The results were correlated with clinicopathological parameters and the prognostic value was determined by multivariate analysis. Strong Rb and moderate-high cyclin E immunoreactivity in carcinomas were weakly associated with high expression of the proliferation marker Ki67. By Cox's multivariate analysis, advanced stage (p=0.013), strong Rb expression (p=0.006), and negative-weak p21 staining (p=0.011) were independent prognostic indicators of short overall survival, indicating an apparently paradoxical role of the retinoblastoma protein in these tumors. In addition, trends pointing to an association of higher age (p=0.067) and positive cyclin E immunoreactivity (p=0.093) with an unfavorable prognosis were observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Carcinoma / metabolism*
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Cell Cycle Proteins / biosynthesis*
  • Cyclin D2
  • Cyclin E / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclins / biosynthesis
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / biosynthesis
  • Middle Aged
  • Multivariate Analysis
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Retinoblastoma Protein / biosynthesis
  • Survival Analysis
  • Tumor Suppressor Proteins / biosynthesis


  • Biomarkers, Tumor
  • CCND2 protein, human
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin D2
  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Ki-67 Antigen
  • Retinoblastoma Protein
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27