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Prognostic Significance of a Novel Hypoxia-Regulated Marker, Carbonic Anhydrase IX, in Invasive Breast Carcinoma

From the Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia; Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada; Imperial Cancer Research Fund Molecular Oncology Laboratory, University of Oxford, Institute of Molecular Medicine and Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, and Welcome Trust, University of Oxford, Churchill Hospital, Oxford, United Kingdom; and Institute of Virology, Slovak Academy of Sciences, Slovak Republic.

Address reprint requests to Adrian L. Harris, MD, Imperial Cancer Research Fund Molecular Oncology Laboratory, University of Oxford, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom; email: aharris.lab{at}lcrf.lcnet.uk

PURPOSE: To assess the frequency of expression and the prognostic significance of a hypoxia-regulated marker, carbonic anhydrase IX (CA IX), in a cohort of patients with invasive breast cancer.

PATIENTS AND METHODS: CA IX expression was evaluated by immunohistochemistry with a murine monoclonal antibody, M75, in a series of 103 women treated surgically for invasive breast cancer. The majority of patients were treated 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 analyses.

RESULTS: CA IX expression was present in 49 (48%) of 103 cases. The level of CA IX expression was found to be significantly associated with tumor necrosis (P < .001), higher grade (P = .02), and negative estrogen receptor status (P < .001). Furthermore, CA IX expression was associated with a higher relapse rate (P = .004) and a worse overall survival (P = .001). By multivariate 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 survival and overall survival in an unselected cohort of patients with invasive breast carcinoma. The potential role of CA IX as a marker of hypoxia within breast carcinomas was also indicated by a significant association with necrosis. Further work assessing its prognostic significance in breast cancer is warranted, particularly interactions with radiotherapy and chemotherapy resistance.

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