High frequency of putative ovarian cancer stem cells with CD44/CK19 coexpression is associated with decreased progressionfree intervals in patients with recurrent epithelial ovarian cancer. Reprod Sci

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 putativeOCSCs (CD44þCK19þOCSCs) with the clinicopathologic features and the prognostic value in patients with recurrent advanced stage EOC. Methods: A retro-spective 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 frequencyordensity ofCD44þCK19þOCSCs inEOC.Results:Themean follow-up timewas 42.8+ 27.1months.High frequency of EOC cells with CD44þ or CD44þ/CK19þ 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 (CD44þ and CK19þ) in epithelial ovarian tumors correlates with short progression-free intervals