Low ERCC1 mRNA and protein expression are associated with worse survival in cervical cancer patients treated with radiation alone

• Published in: Radiotherapy and oncology 2010-11, Vol.97 (2), p.352-359
• Main Authors: Doll, Corinne M, Prystajecky, Michael, Eliasziw, Misha, Klimowicz, Alexander C, Petrillo, Stephanie K, Craighead, Peter S, Hao, Desiree, Diaz, Roman, Lees-Miller, Susan P, Magliocco, Anthony M
• Format: Article
• Language: English
• Subjects: Cervical cancer; Disease-Free Survival; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Endonucleases - genetics; Endonucleases - metabolism; ERCC1; Female; Gene Expression Regulation, Neoplastic; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Neoplasm Staging; Prognosis; Radiation therapy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Uterine Cervical Neoplasms - mortality; Uterine Cervical Neoplasms - radiotherapy
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2010.08.019

Abstract Purpose To evaluate the association of excision repair cross-complementation group 1 (ERCC1) expression, using both mRNA and protein expression analysis, with clinical outcome in cervical cancer patients treated with radical radiation therapy (RT). Experimental design Patients ( n = 186) with locally advanced cervical cancer, treated with radical RT alone from a single institution were evaluated. Pre-treatment FFPE biopsy specimens were retrieved from 112 patients. ERCC1 mRNA level was determined by real-time PCR, and ERCC1 protein expression (FL297, 8F1) was measured using quantitative immunohistochemistry (AQUA®). The association of ERCC1 status with local response, 10-year disease-free (DFS) and overall survival (OS) was analyzed. Results ERCC1 protein expression levels using both FL297 and 8F1 antibodies were determined for 112 patients; mRNA analysis was additionally performed in 32 patients. Clinical and outcome factors were comparable between the training and validation sets. Low ERCC1 mRNA expression status was associated with worse OS (17.9% vs 50.1%, p = 0.046). ERCC1 protein expression using the FL297 antibody, but not the 8F1 antibody, was significantly associated with both OS ( p = 0.002) and DFS ( p = 0.010). After adjusting for pre-treatment hemoglobin in a multivariate analysis, ERCC1 FL297 expression status remained statistically significant for OS [HR 1.9 (1.1–3.3), p = 0.031]. Conclusions Pre-treatment tumoral ERCC1 mRNA and protein expression, using the FL297 antibody, are predictive factors for survival in cervical cancer patients treated with RT, with ERCC1 FL297 expression independently associated with survival. These results identify a subset of patients who may derive the greatest benefit from the addition of cisplatin chemotherapy.