Clear cell carcinoma has an expression pattern of cell cycle regulatory molecules that is unique among ovarian adenocarcinomas

Cancer. 1999 Feb 1;85(3):669-77. doi: 10.1002/(sici)1097-0142(19990201)85:3<669::aid-cncr17>;2-f.


Background: The purpose of this study was to identify biologic differences between ovarian clear cell carcinoma and other ovarian adenocarcinomas by comparing the expression of cell cycle regulatory molecules and by analyzing the survival of the patients.

Methods: In 51 cases of epithelial ovarian carcinoma, the expression of the cell proliferation marker Ki-67 and that of the cell cycle regulatory molecules p53, p16, p21, p27, cyclin E, and cyclin A was studied using immunohistochemical techniques. The correlations among clinical stage, histologic subtype, labeling index for Ki-67, and expression of these cell cycle regulators were examined statistically. Multivariate survival analysis was performed using these factors in the Cox proportional hazards model.

Results: Clear cell carcinoma revealed such trends as low expression of both p53 and cyclin A and significantly increased expression of both p21 and cyclin E (compared with the other histologic subtypes). In all ovarian carcinomas, a very strong positive correlation (correlation coefficient 0.79; P < 0.0001) between p53 positive staining and cyclin A positive staining and a weak positive correlation (correlation coefficient 0.47; P < 0.01) between p21 positive staining and cyclin E positive staining were recognized at the level of expression of cell cycle regulatory molecules. Clinical stage was the only independent predictive factor for the survival of the patients.

Conclusions: Among ovarian adenocarcinomas, clear cell carcinoma exhibits a unique pattern of expression of cell cycle regulatory molecules, though in this study the survival of the patients did not correlate with histologic subtype, only with clinical stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma, Clear Cell / metabolism*
  • Adenocarcinoma, Clear Cell / mortality
  • Adenocarcinoma, Mucinous / metabolism
  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Carcinoma, Endometrioid / metabolism
  • Cell Cycle Proteins / metabolism*
  • Cyclin A / metabolism
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • Cystadenocarcinoma, Serous / metabolism
  • Female
  • Humans
  • Ki-67 Antigen / metabolism
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Muscle Proteins*
  • Neoplasm Proteins / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Proportional Hazards Models
  • Survival Analysis
  • Tumor Suppressor Protein p53 / metabolism


  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin A
  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Ki-67 Antigen
  • Microfilament Proteins
  • Muscle Proteins
  • Neoplasm Proteins
  • Tagln protein, mouse
  • Tumor Suppressor Protein p53