Cancer Stem Cell Properties as Factors Predictive of Chemoresistance in Neoadjuvantly-treated Patients with Ovarian Cancer.

BACKGROUND/AIM: The nuclear factor erytheroid 2-related factor 2-kelch-like ECH-associated protein (NRF2-KEAP1) system and stem cell-like cancer cells are associated with platinum resistance in ovarian cancer. Our objective was to investigate the possible association between platinum resistance, cellular redox-state regulation and stem cell properties in ovarian cancer.

PATIENTS AND METHODS: Thirty-eight patients with epithelial ovarian cancer were included. All patients had undergone primary diagnostic laparoscopy, platinum-based neoadjuvant chemotherapy, and debulking surgery. Tumor samples were analyzed for NRF2, KEAP1, protein deglycase 1 (DJ1/PARK7), cluster of differentiation molecules 44 (CD44) and 117 (CD117) and aldehyde dehydrogenase 1 (ALDH1) by immunohistochemistry.

RESULTS: Positive pre-treatment expression of CD44 (p=0.013) and stable/increased post-therapy CD44 expression were associated with platinum resistance (p=0.001). Negative pre-treatment expression of cytoplasmic ALDH1 predicted sensitivity to platinum (p=0.017). Pre-treatment nuclear KEAP1 expression was greater in stage II-III cancer (p=0.0003). After neoadjuvant treatment, all samples were nuclear KEAP1-positive (p=0.025) and increased nuclear KEAP1 expression was associated with higher tumor stage (p=0.0001).

CONCLUSION: CD44 and cytoplasmic ALHD1 could be potential indicators of platinum resistance during neoadjuvant chemotherapy for ovarian cancer.