title: Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer.
abstract: Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes.
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Tiyasha H
authors.initials: TH
authors.lastname: Ayub
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Mignon-Denise
authors.initials: MD
authors.lastname: Keyver-Paik
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Debald
authors.affiliation: Institute of Pathology, Center for Integrated Oncology, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Babak
authors.initials: B
authors.lastname: Rostamzadeh
authors.affiliation: Institute of Pathology, Center for Integrated Oncology, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Thore
authors.initials: T
authors.lastname: Thiesler
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Schröder
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, Center for Integrated Oncology, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Barchet
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Abramian
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Kaiser
authors.affiliation: Institute of Pathology, Center for Integrated Oncology, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Walther
authors.initials: W
authors.lastname: Kuhn
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Kübler
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D051927:CD24 Antigen / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D010455:Peptides / Q000378:metabolism; D017671:Platinum Compounds / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome; D014410:Tumor Stem Cell Assay
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D051927:CD24 Antigen; C497889:CD24 protein, human; D006023:Glycoproteins; D007527:Isoenzymes; C000606023:PROM1 protein, human; D010455:Peptides; D017671:Platinum Compounds; D043823:Taxoids; C080625:taxane; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D019009:Proto-Oncogene Proteins c-kit
keywords: ALDH1; cancer stem-like cell; ovarian cancer; predictive marker; prognostic marker