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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

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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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Second Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, China

    Ming Liu MD & Xue Xiang MD

  2. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, USA

    Ming Liu MD, Gil Mor MD, PhD, Thomas Rutherford MD, PhD, Gang Yin PhD, Jennie Holmberg MSc, Ayesha Alvero MD & Dan-Arin Silasi MD

  3. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA

    Huan Cheng PhD, Pei Hui MD & David L. Rimm MD, PhD

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  1. Ming Liu MD
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  2. Gil Mor MD, PhD
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Correspondence to Dan-Arin Silasi MD.

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Liu, M., Mor, G., Cheng, H. et al. 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. 20, 605–615 (2013). https://doi.org/10.1177/1933719112461183

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