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Carbonic Anhydrase IX Is Not an Independent Predictor of Outcome for Patients With Clear Cell Renal Cell Carcinoma

Bradley C. Leibovich, Yuri Sheinin, Christine M. Lohse, R. Houston Thompson, John C. Cheville, Jan Zavada, Eugene D. Kwon

From the Departments of Urology, Health Sciences Research, Laboratory Medicine and Pathology, and Immunology, Mayo Medical School and Mayo Clinic, Rochester, MN; and the Institute of Organic Chemistry and Biochemistry, Prague, Czech Republic

Address reprint requests to Eugene D. Kwon, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: kwon.eugene{at}mayo.edu

Purpose Expression of carbonic anhydrase IX (CAIX) has been reported to be an independent predictor of outcome and is being investigated as a therapeutic target for patients with clear cell renal cell carcinoma (ccRCC). We attempted to validate the prognostic utility of CAIX expression using a large cohort of ccRCC patients with long-term follow-up.

Patients and Methods We identified 730 patients with unilateral, sporadic ccRCC treated surgically between 1990 and 1999. Anti-CAIX monoclonal antibody (clone M75) was used, and tumor specimens were blindly scored for expression levels. Associations of CAIX expression with RCC death were evaluated using Cox proportional hazards regression models.

Results There were 241 RCC deaths and a median of 9.4 years of follow-up for patients still under observation. CAIX was expressed in 708 (97.0%) of the specimens; 163 tumors (22.3%) exhibited low ( 85% tumor cells positive) expression, and 567 (77.7%) exhibited high (> 85% tumor cells positive) expression. Univariately, low CAIX expression was associated with increased risk of RCC death relative to high expression (risk ratio = 1.65; P < .001). However, low CAIX expression was not associated with RCC death after adjusting for nuclear grade or coagulative tumor necrosis. Additionally, we observed CAIX expression in a number of extrarenal organs.

Conclusion CAIX is strongly expressed by ccRCC. Although CAIX is associated with outcome in patients with ccRCC, it is not an independent prognostic marker. Furthermore, CAIX expression is apparent in extrarenal organs. As such, exploitation of CAIX as a prognostic marker and therapeutic target merits additional consideration.

Supported in part by the Richard M. Schulze Family Foundation, the Commonwealth Foundation for Cancer Research, and the Helen and Martin Kimmel Foundation.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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Related Correspondence

• Carbonic Anhydrase IX As a Predictive Biomarker for Clear Cell Renal Cell Carcinoma
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