Aldehyde Dehydrogenase 1 Expression Predicts Chemoresistance and Poor Clinical Outcomes in Patients with Locally Advanced Cervical Cancer Treated with Neoadjuvant Chemotherapy Prior to Radical Hysterectomy

• Published in: Annals of surgical oncology 2016, Vol.23 (1), p.163-170
• Main Authors: Xie, Qingsheng, Liang, Jinxiao, Rao, Qunxian, Xie, Xiaofei, Li, Ruixin, Liu, Yunyun, Zhou, Hui, Han, Jingjing, Yao, Tingting, Lin, Zhongqiu
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biomarkers, Tumor - metabolism; Carboplatin - administration & dosage; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - enzymology; Carcinoma, Squamous Cell - secondary; Cervical cancer; Cisplatin - administration & dosage; Combined Modality Therapy; Drug Resistance, Neoplasm; Female; Fluorouracil - administration & dosage; Follow-Up Studies; Gynecologic Oncology; Humans; Hysterectomy; Immunoenzyme Techniques; Isoenzymes - metabolism; Lymphatic Metastasis; Medicine; Medicine & Public Health; Neoadjuvant Therapy - adverse effects; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Recurrence, Local - chemically induced; Neoplasm Recurrence, Local - enzymology; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Oncology; Prognosis; Retinal Dehydrogenase - metabolism; Surgery; Surgical Oncology; Survival Rate; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - enzymology; Uterine Cervical Neoplasms - pathology
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-015-4555-7

Background Neoadjuvant chemotherapy (NAC) is an important treatment strategy for cervical cancer; however, few predictive markers of the response to NAC exist. Aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, is associated with chemoresistance in a variety of cancers. This study attempted to investigate the value of ALDH1 as a predictive marker of chemosensitivity and its prognostic value in cervical cancer patients treated with NAC. Methods Immunohistochemistry was used to evaluate ALDH1 expression in matched pre- and post-NAC tumor samples from 52 patients with cervical cancer. Kaplan–Meier analysis and a Cox proportional hazards regression model were applied to determine overall survival (OS) and disease-free survival (DFS). Results Fourteen patients (26.9 %) had ALDH1-positive tumors pre-NAC, and ALDH1 expression pre-NAC was significantly associated with a low clinical chemotherapy response rate and clinical non-response. Twenty-two patients (42.3 %) had ALDH1-positive tumors post-NAC, and ALDH1 expression post-NAC was associated with poor DFS and OS (both p  = 0.004). Multivariate analysis revealed that ALDH1 expression post-NAC was an independent prognostic factor for OS (hazard ratio 3.513; p  = 0.033). Moreover, we observed that ALDH1 expression was increased after NAC in 18 patients (36.7 %). Increased levels of ALDH1 expression after NAC predicted poor DFS and OS ( p  = 0.013 and p  = 0.08, respectively). Conclusions Our findings suggest that ALDH1 expression pre-NAC may be a predictive marker for response to NAC, and ALDH1 expression post-NAC could be a prognostic marker for cervical cancer.