title: 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.
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).
  
  
  CONCLUSIONS
  Our findings suggest that high frequency of OCSCs (CD44+ and CK19+) in epithelial ovarian tumors correlates with short progression-free intervals.
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
authors.forename: Huan
authors.initials: H
authors.lastname: Cheng
authors.forename: Xue
authors.initials: X
authors.lastname: Xiang
authors.forename: Pei
authors.initials: P
authors.lastname: Hui
authors.forename: Thomas
authors.initials: T
authors.lastname: Rutherford
authors.forename: Gang
authors.initials: G
authors.lastname: Yin
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
authors.forename: Jennie
authors.initials: J
authors.lastname: Holmberg
authors.forename: Ayesha
authors.initials: A
authors.lastname: Alvero
authors.forename: Dan-Arin
authors.initials: DA
authors.lastname: Silasi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D000077216:Carcinoma, Ovarian Epithelial; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D053539:Keratin-19 / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000737:chemistry* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D053539:Keratin-19