Prognostic Significance of Membranous Carbonic Anhydrase IX Expression in Patients with Nonmetastatic Clear Cell Renal Cell Carcinoma of Different Tumor Stages.

There are paradoxical results regarding whether carbonic anhydrase IX (CAIX) is a prognostic biomarker for patients with clear cell renal cell carcinoma (ccRCC). The objective of this study was to evaluate prognostic significance of CAIX in nonmetastatic ccRCC patients of different stages. This is a retrospective study on 1263 patients with nonmetastatic ccRCC from January 2005 to June 2018. Patients were stratified into eight subgroups (pT1a, pT1b, pT2a, pT2b, pT3a, pT3b, pT3c, and pT4) according to the 2016 TNM classification system. Immunohistochemical staining of membranous CAIX was quantified. Cancer-specific survival (CSS) rates in patients with high (>85%) and low (<85%) CAIX expressions were compared by Kaplan-Meier curves with log-rank test. There were 220 tumors (17.42%) with low CAIX expression and 1043 tumors (82.58%) with high CAIX expression. The cumulative CSS rates were statistically significant between all patients with low and high CAIX expression (-value <0.001). In pT2a, pT2b, and pT3a subgroups, the patients with low CAIX expression exhibited markedly decreased cumulative CSS rates compared to patients with high CAIX expression (-value <0.05). Univariable and multivariable Cox regression analysis showed that CAIX expression was an independent predictor of prognosis in patients with pT2a, pT2b, and pT3a ccRCC (-value <0.05), rather than in all nonmetastatic patients. CAIX expression is of independent prognostic value for ccRCC patients in pT2a, pT2b, and pT3a stages. CAIX expression combined with tumor stage would further improve risk stratification of nonmetastatic ccRCC patients and provide directions for therapies.