Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer

Tiyasha H. Ayub; Mignon-Denise Keyver-Paik; Manuel Debald; Babak Rostamzadeh; Thore Thiesler; Lars Schröder; Winfried Barchet; Alina Abramian; Christina Kaiser; Glen Kristiansen; Walther Kuhn; Kirsten Kübler

doi:10.18632/oncotarget.4103

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Research Papers:

Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer

Tiyasha H. Ayub, Mignon-Denise Keyver-Paik, Manuel Debald, Babak Rostamzadeh, Thore Thiesler, Lars Schröder, Winfried Barchet, Alina Abramian, Christina Kaiser, Glen Kristiansen, Walther Kuhn and Kirsten Kübler _

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Oncotarget. 2015; 6:16437-16448. https://doi.org/10.18632/oncotarget.4103

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Abstract

Tiyasha H. Ayub1,*, Mignon-Denise Keyver-Paik1,*, Manuel Debald1, Babak Rostamzadeh2, Thore Thiesler2, Lars Schröder1, Winfried Barchet3, Alina Abramian1, Christina Kaiser1, Glen Kristiansen2, Walther Kuhn1 and Kirsten Kübler1

1 Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Bonn, Germany

2 Institute of Pathology, Center for Integrated Oncology, Bonn, Germany

3 Institute of Clinical Chemistry and Clinical Pharmacology, Center for Integrated Oncology, Bonn, Germany

* These authors have contributed equally to this work

Correspondence to:

Kirsten Kübler, email:

Keywords: ovarian cancer, predictive marker, prognostic marker, ALDH1, cancer stem-like cell

Received: March 01, 2015 Accepted: April 08, 2015 Published: May 11, 2015

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.

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PII: 4103

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Research Papers:

Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer

Abstract