This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leibovich, B. C. Articles by Kwon, E. D. Search for Related Content PubMed PubMed Citation Articles by Leibovich, B. C. Articles by Kwon, E. D. Related Articles Related Correspondence

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.

Related Correspondence

• Carbonic Anhydrase IX As a Predictive Biomarker for Clear Cell Renal Cell Carcinoma
  Allan J. Pantuck, Tobias Klatte, David Seligson, Michael Atkins, and Arie Belldegrun
  JCO 2008 26: 3105-3107 [Full Text]

This article has been cited by other articles:

				A. H. Brouwers, P. F.A. Mulders, and W. J.G. Oyen Carbonic Anhydrase IX Expression in Clear Cell Renal Cell Carcinoma and Normal Tissues: Experiences From (Radio) Immunotherapy J. Clin. Oncol., August 1, 2008; 26(22): 3808 - 3809. [Full Text] [PDF]

				P. Skapa, L. Hyrsl, J. Zavada, J. Soukup, and J. Zamecnik Carbonic Anhydrase IX Expression in Clear Cell Renal Cell Carcinomas Negatively Correlates With the Proportion of the Granular Cell Component J. Clin. Oncol., August 1, 2008; 26(22): 3809 - 3811. [Full Text] [PDF]

				B. C. Leibovich, Y. Sheinin, C. M. Lohse, R. H. Thompson, J. C. Cheville, J. Zavada, and E. D. Kwon In Reply J. Clin. Oncol., August 1, 2008; 26(22): 3811 - 3812. [Full Text] [PDF]

				A. J. Pantuck, T. Klatte, D. Seligson, M. Atkins, and A. Belldegrun Carbonic Anhydrase IX As a Predictive Biomarker for Clear Cell Renal Cell Carcinoma J. Clin. Oncol., June 20, 2008; 26(18): 3105 - 3107. [Full Text] [PDF]

				B. C. Leibovich, Y. Sheinin, C. M. Lohse, R. H. Thompson, J. C. Cheville, J. Zavada, and E. D. Kwon In Reply J. Clin. Oncol., June 20, 2008; 26(18): 3107 - 3109. [Full Text] [PDF]

				W. K. Rathmell, W. M. Stadler, and B. I. Rini Rational Therapeutic Choices and Strategies for Patients with Metastatic Renal Cancer ASCO Educational Book, January 1, 2008; 2008(1): 192 - 198. [Abstract] [Full Text] [PDF]