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

Abstract

// Tiyasha H. Ayub 1,* , Mignon-Denise Keyver-Paik 1,* , Manuel Debald 1 , Babak Rostamzadeh 2 , Thore Thiesler 2 , Lars Schröder 1 , Winfried Barchet 3 , Alina Abramian 1 , Christina Kaiser 1 , Glen Kristiansen 2 , Walther Kuhn 1 and Kirsten Kübler 1 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.