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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

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Title: 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
Authors: Ruscito, I
Castillo-Tong, DC
Vergote, I
Ignat, I
Stanske, M
Vanderstichele, A
Ganapathi, RN
Glajzer, J
Kulbe, H
Trillsch, F
Mustea, A
Kreuzinger, C
Panici, PB
Gourley, C
Gabra, H
Kessler, M
Sehouli, J
Darb-Esfahani, S
Braicu, EI
Item Type: Journal Article
Abstract: 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+ and ALDH1+ respectively. CD133+ and ALDH1+ 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 + 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.
Issue Date: 16-May-2017
Date of Acceptance: 10-Apr-2017
URI: http://hdl.handle.net/10044/1/50572
DOI: https://dx.doi.org/10.1016/j.ejca.2017.04.016
ISSN: 0959-8049
Publisher: Elsevier
Start Page: 214
End Page: 225
Journal / Book Title: European Journal of Cancer
Volume: 79
Copyright Statement: © 2017 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
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
CHEMOTHERAPY
METAANALYSIS
MARKER
CARCINOMA
AC133 Antigen
Adult
Aged
Antineoplastic Agents
BRCA2 Protein
Biomarkers, Tumor
Clonal Evolution
Female
Humans
Isoenzymes
Middle Aged
Neoplasm Recurrence, Local
Neoplasm, Residual
Neoplasms, Glandular and Epithelial
Neoplastic Stem Cells
Ovarian Neoplasms
Platinum Compounds
Retinal Dehydrogenase
Survival Analysis
Ubiquitin-Protein Ligases
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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