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

Abstract

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. 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. 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. 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.