Carbonic Anhydrase IX Is an Independent Prognostic Predictor for Clinically Localized Clear Cell Renal Cell Carcinoma.
Huiying He, Paul Elson, Hakan Aydin, Steve Campbell, Brian Rini, Cristina Magi-Galluzzi, Ming Zhou. Cleveland Clinic; Peking University, Health Science Center, Beijing, China
Background: Carbonic anhydrase IX (CAIX) is a membrane glycoprotein regulating pH and serves as a marker for hypoxia. It is expressed in the majority of clear cell renal cell carcinomas (CCRCC) and high level of expression (in >85% of tumor cells) has been reported to correlate with better prognosis in patients with metastatic CCRCC. Its prognostic significance in localized CCRCC, however, is uncertain due to conflicting results from only a few studies. We investigated the expression and prognostic significance of CAIX in a large cohort of localized CCRCC with long-term follow-up.
Design: A tissue microarray was constructed from 552 unilateral, clinically localized CCRCC treated surgically between 1990 and 2003 and was immunostained for CAIX expression (antibody clone NB100-417). The membranous CAIX staining was evaluated as positive. The staining intensity (0-negative, 1-weak, 2-moderate, 3-strong) and the percentage of cells with each staining intensity were recorded. A composite score was calculated by adding together the products of each staining intensity and its corresponding percentage of positive cells. The CAIX expression, measured as composite score, maximum intensity and percentage of positive cells, was correlated with pathological parameters and clinical outcomes.
Results: CAIX was expressed in 80.4% (444/552) cases with staining intensity 1, 2 and 3 seen in 16.5%, 42.4% and 21.5% of cases. The median percentage of positive cells was 67% (range 2-100%) and the median composite score was 90 (range 4-300). CAIX composite score inversely correlated with Fuhrman nuclear grade and necrosis (p=0.02 and 0.04). In univariate analysis, presence of strong staining intensity (staining intensity 3) and percentage of positive cells were both associated with overall survival, p=0.002 and 0.004, respectively. Using the Cox proportional hazards model, the presence of any strong staining (intensity 3) was a significant independent predictor for better survival (hazard Ratio=2.82, p=0.003) as were the other known bad prognosis markers including age, presence of perinephric fat invasion, nuclear grade, and necrosis.
Conclusions: The CAIX expression is associated with overall survival in patients with localized CCRCC. Strong CAIX expression is significantly associated with better survival independent of other known clinicopathological parameters. Our study confirms the prognostic significance of CAIX expression in clinically localized CCRCC.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 117, Wednesday Morning