Prognostic significance of a novel hypoxia-regulated marker, carbonic anhydrase IX, in invasive breast carcinoma

Purpose: To assess the frequency of expression and the prognostic significa nce of a hypoxia-regulated marker, carbonic anhydrase IX (CA IX), in a coho rt of patients with invasive breast cancer. Patients and Methods: CA IX expression was evaluated by immunohistochemistr y with a murine monoclonal antibody, M75, in a series of 103 women treated surgically for invasive breast cancer. The majority of patients were treate d with adjuvant hormonal or chemotherapy. The frequency of CA IX expression , its association with recognized prognostic factors, and the relationship with outcome was evaluated by univariate and multivariate statistical analy ses. Results: CA IX expression was present in 49 (48%) of 103 cases. The level o f CA IX expression was found to be significantly associated with tumor necr osis (P < .001), higher grade (P = .02), and negative estrogen receptor sta tus (P < .001). Furthermore, CA IX expression was associated with a higher relapse rate (P = .004) and a worse overall survival (P = .001). By multiva riate analysis, CA IX was also shown to be an independent predictive factor for overall survival (hazard ratio, 2.61; 95% confidence interval, 1.01 to 6.75, P = .05). Conclusion: CA IX expression was associated with worse relapse-free surviva l and overall survival in an unselected cohort of patients with invasive br east carcinoma. The potential role of CA IX as a marker of hypoxia within b reast carcinomas was also indicated by a significant association with necro sis. Further work assessing its prognostic significance in breast cancer is warranted, particularly interactions with radiotherapy and chemotherapy re sistance. J Clin Oncol 19:3660-3668. (C) 2001 by American Society of Clinical Oncolog y.