High frequency of putative ovarian cancer stem cells with CD44/CK19 coexpression is associated with decreased progression-free intervals in patients with recurrent epithelial ovarian cancer

Reprod Sci. 2013 May;20(5):605-15. doi: 10.1177/1933719112461183. Epub 2012 Nov 20.

Abstract

Objective: Epithelial ovarian cancer (EOC) cells with CD44 and CK19 coexpression may represent a subset of ovarian cancer stem cells (OCSCs). This study was conducted to evaluate the correlation of the frequency of putative OCSCs (CD44 + CK19 + OCSCs) with the clinicopathologic features and the prognostic value in patients with recurrent advanced stage EOC.

Methods: A retrospective study was carried out on 33 patients with EOC and a uniformly treated tissue microarray was constructed. A multiplexed, immunofluorescence-based method of automated in situ quantitative measurement of protein analysis was used for evaluation of the frequency or density of CD44 + CK19 + OCSCs in EOC.

Results: The mean follow-up time was 42.8 ± 27.1 months. High frequency of EOC cells with CD44+ or CD44+/CK19+ was associated with chemoresistance (P = .033 and P = .02, respectively). Using K-M analysis with log-rank test, a high frequency of putative OCSCs was associated with short disease-free interval (7.9 months vs 20.9 months, P = .019). In univariable analysis, the frequency of OCSCs, International Federation of Gynecology and Obstetrics stage and residual tumor volume were significant predictor variables and were entered into multivariable analysis (P = .019, .037, and .005, respectively). Although no independent significant predictor was found, the frequency of putative OCSCs was the most promising predictor variable compared with the other 2 variables (hazard ratio = 2.344, P = .052).

Conclusion: Our findings suggest that high frequency of OCSCs (CD44+ and CK19+) in epithelial ovarian tumors correlates with short progression-free intervals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Ovarian Epithelial
  • Disease Progression
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Hyaluronan Receptors / analysis*
  • Kaplan-Meier Estimate
  • Keratin-19 / analysis*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / chemistry
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / chemistry
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology
  • Neoplastic Stem Cells / chemistry*
  • Neoplastic Stem Cells / pathology
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • CD44 protein, human
  • Hyaluronan Receptors
  • Keratin-19