Exploring the clonal evolution of CD133/aldehyde-dehydrogenase-1 (ALDH1)-positive cancer stem-like cells from primary to recurrent high-grade serous ovarian cancer (HGSOC). A study of the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium

被引：28

作者：

Ruscito, Ilary ^{[1
,2
,3
]}

Castillo-Tong, Dan Cacsire ^{[4
]}

Vergote, Ignace ^{[5
]}

Ignat, Iulia ^{[1
]}

Stanske, Mandy ^{[6
]}

Vanderstichele, Adriaan ^{[5
]}

Ganapathi, Ram N. ^{[7
]}

Glajzer, Jacek ^{[1
]}

Kulbe, Hagen ^{[1
]}

Trillsch, Fabian ^{[8
,9
]}

Mustea, Alexander ^{[10
]}

Kreuzinger, Caroline ^{[4
]}

Panici, Pierluigi Benedetti ^{[2
]}

Gourley, Charlie ^{[11
]}

Gabra, Hani ^{[12
]}

Kessler, Mirjana ^{[13
]}

Sehouli, Jalid ^{[1
]}

Darb-Esfahani, Silvia ^{[6
]}

Braicu, Elena Ioana ^{[1
]}

机构：

[1] Charite Univ Med Berlin, Dept Gynecol, European Competence Ctr Ovarian Canc, Campus Virchow Klinikum, Augustenburger Pl 1, D-13353 Berlin, Germany

[2] Sapienza Univ Rome, Dept Gynecol Obstet & Urol, Rome, Italy

[3] Sapienza Univ Rome, Dept Expt Med, Rome, Italy

[4] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Gynecol, Waehringer Guertel 18-20, A-1090 Vienna, Austria

[5] Katholieke Univ Leuven, Div Gynaecol Oncol, Leuven Canc Inst, Dept Gynaecol & Obstet,Univ Ziekenhuizen Leuven, Herestr 49, B-3000 Leuven, Belgium

[6] Charite, Inst Pathol, Campus Mitte, Berlin, Germany

[7] Carolinas HealthCare Syst, Levine Canc Inst, Dept Canc Pharmacol, Charlotte, NC USA

[8] Univ Munich, Dept Gynecol & Obstet, Marchioninistr 15, Munich, Germany

[9] Univ Med Ctr Hamburg Eppendorf, Dept Gynecol & Gynecol Oncol, Martinistr 46, Hamburg, Germany

[10] Univ Med Greifswald, Dept Gynecol & Obstet, Greifswald, Germany

[11] Univ Edinburgh, Canc Res UK Ctr, Nicola Murray Ctr Ovarian Canc Res, MRC,IGMM Western Gen Hosp, Crewe Rd South, Edinburgh EH4 2XR, Midlothian, Scotland

[12] Imperial Coll London, Dept Surg & Canc, Ovarian Canc Action Res Ctr, London, England

[13] Max Planck Inst Infect Biol, Dept Mol Biol, Berlin, Germany

来源：

EUROPEAN JOURNAL OF CANCER | 2017年 / 79卷

关键词：

Ovarian cancer; CD133; ALDH1; Aldehyde dehydrogenase-1; Cancer stem-like cell; BRCA; Prognosis; Survival; ALDEHYDE DEHYDROGENASE 1; ALDH1; EXPRESSION; BRCA2; MUTATIONS; CLINICAL-TRIALS; POOR-PROGNOSIS; CD133; CHEMOTHERAPY; METAANALYSIS; MARKER; CARCINOMA;

D O I：

10.1016/j.ejca.2017.04.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. Methods: Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels. Expression profiles were also correlated with patients' clinicopathological and survival data. Results: Some 49.1% of the patient population (55/112) and 37.5% (42/112) pOCs were CD133+ andALDH1 vertical bar respectively. CD133 vertical bar and ALDH1 vertical bar samples were detected in 33.9%(38/112) and 36.6% (41/112) rOCs. CD133/ALDH1 coexpression was observed in 23.2% (26/112) and 15.2% (17/112) of pOCs and rOCs respectively. Pairwise analysis showed a significant shift of CD133 staining from higher (pOCs) to lower expression levels (rOCs) (p < 0.0001). Furthermore, all CD133 vertical bar pOC patients were International Federation of Gynaecology and Obstetrics (FIGO)-stage III/IV (p < 0.0001) and had significantly worse progression-free interval (PFI) (p = 0.04) and overall survival (OS) (p = 0.02). On multivariate analysis, CD133/ALDH1 coexpression in pOCs was identified as independent prognostic factor for PFI (HR: 1.64; 95% CI: 1.03 -2.60; p = 0.036) and OS (HR: 1.71; 95% CI: 1.01-2.88; p = 0.045). Analysis on 52 pts patients with known somatic BRCA status revealed that BRCA mutations did not influence CSC biomarker expression. Conclusions: The study showed that CD133/ALDH1 expression impacts HGSOC patients' survival and first suggests that CSCs might undergo phenotypic change during the disease course similarly to non stem-like cancer cells, providing also a first evidence that there is no correlation between CSCs and BRCA status. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：214 / 225

页数：12

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