Prognostic Significance Of Carbonic Anhydrase IX Expression In Clear Cell Renal Cell Carcinoma

Objective: To evaluate the prognostic significance of carbonic anhydrase IX (CA IX) expression in patients with clear cell carcinoma renal cell carcinoma (ccRCC).Methods:Our study comprised samples from 120 patiens (median age at 57 years,range 18-75) with ccRCC who underwent nephroureterectomy at Fujian Provincial Hospital between May 2002 and March 2010.All specimens were pathologically confirmed.Patients included 76 men and 44 women. According to the WHO(1997) histologic Fuhrman grading system and AJCC of TNM(2002) classification system,they were:41 cases of I stage,57 cases of II stage,22 cases III-IV stage;48 cases of I grade , 56 cases of II grade, 16 cases of III-IV grade.Lymph node metastasis was found in 12 samples, 16 cases with venous tumor embolus.CA IX expression in a cohort of 120 patients with ccRCC was evaluated by P-V immunohistochemistry with a rabbit CA IX polyclonal antibody, 25 normal kidney tissue was used as a control.All patients of the survival and postoperative adjuvant treatment by telephone, outpatient follow-up, letters follow-up and door-to-door follow-up.The relationship between CA IX expression and prognosis was analyzed by univariate and multiple-factor analysis (Cox regression model). The primary end point was cancer specific survival.Results: 112(93.3%) patients were followed-up , median follow-up time was 45 months (range 6 to 94 months),75 patients were alive without evidence of tumor recurrence,3 patients survived with tumour recurrence, 34 patients died,among them 28 died of cancer.CA IX expression was negative in all nomal renal tissue. High CA IX expression was observed in 89(74.2%) patients, among high expression group, 82 patients were followed-up,disease free survival was 62/82(75.6%), 2(2.4%) patients survived with tumor recurrence, 18 (22.0%)patients died, 13(15.9%)of them died of cancer, tumor recurrence and (or) metastasis occurred in 9(11.0%) patients, median survival was 92 months in this high expression group. Low CA IX expression was observed in 31(25.8%) patients, among low expression group, 30 patients were followed-up, disease free survival was 13/30(43.3%), 1(3.3%) patients survived with tumor recurrence, 16(53.3%) patients died, 15(50.0%) of them died of cancer, tumor recurrence and (or) metastasis occurred in 8(26.7%) patients, median survival was 53 months in this low expression group. Cancer specific survival between CA IX high expression group and low expression group was significant different (P=0.000,χ2=15.950), tumor relapse and (or) metastasis rate were significant different (P=0.040,χ2=4.200). The 1,3,5 and 7 year caner specific survival were 95.2%, 83.9%, 81.2% and 78.2% respectively in high CA IX expression group and 89.5%, 63.9%, 46.8% and 40.1% in low expression group. Multivariate analysis with Cox regression model showed that CA IX expression was a prognostic factor (RR=0.186).Conclusions: High CA IX expression is negatively correlated with postoperative mortality, relapse and (or) metastasis in ccRCC, CA IX expression can be used as a prognostic biomarker.