Expression of cIAP1, a Target for 11q22 Amplification, Correlates with Resistance of Cervical Cancers to Radiotherapy

Abstract

Recently we reported that cIAP1, an inhibitor of apoptosis, is overexpressed through 11q22 amplification in cell lines derived from esophageal squamous cell carcinomas (ESC) and is associated with resistance of ESC to drug-induced apoptosis. In cervical squamous cell carcinoma (CSCC) cell lines, amplification and overexpression of cIAP1 was also observed. CSCC cell lines with cIAP1 amplification showed significant resistance to radiation-induced cell death as compared with lines showing no cIAP1 amplification. Immunohistochemical analysis of 70 primary CSCCs from patients treated only with radiotherapy demonstrated that both overall survival and local recurrence-free survival was significantly poorer among patients with tumors showing high levels of nuclear cIAP1 staining than among patients whose tumors revealed little or no nuclear cIAP1. Multivariate analysis showed nuclear cIAP1 staining to be an independent predictive factor for local recurrence-free survival after radiotherapy among patients with CSCC. These findings demonstrate that cIAP1 may play an important role in the development/progression of CSCC and that cIAP1 could be a novel predictive marker for resistance to radiotherapy in individual CSCC patients.