碳酸酐酶IX表达在肾透明细胞癌预后评估中的价值

Prognostic significance of carbonic anhydrase IX expression in clear cell renal cell carcinoma

目的评估肾透明细胞癌组织中碳酸酐酶IX（CAIX）表达在患者预后判断中的价值。方法应用免疫组织化学P—V方法检测120例肾透明细胞癌和25例正常肾组织石蜡标本中CAIX的表达。以肿瘤特异性生存率作为最终和主要的评估目标。运用Cox回归模型行CAIX表达与预后关系的单因素和多因素分析，以P〈0．05为差异有统计学意义。结果112例（93．3％）获随访，随访6～94个月，中位时间45个月，无瘤生存75例，带瘤生存3例，死亡34例，其中死于肿瘤28例。正常肾组织均不表达CAIX。120例肾透明细胞癌组织中CAIX高表达89例（74．2％），高表达者中获随访82例，无瘤生存62例（75．6％），带瘤生存2例（2．4％），死亡18例（22．0％），死于肿瘤13例（15．9％），复发和（或）转移9例（11．0％），中位生存期为92个月。肾透明细胞癌CAIX低表达31例（25．8％），其中获随访30例，无瘤生存13例（43．3％），带瘤生存1例（3．3％），死亡16例（53．3％），死于肿瘤15例（50．0％），中位生存期为53个月，复发和（或）转移8例（26．7％）。2组肿瘤特异性生存率比较经log—rank检验，差异有统计学意义（P=0．000，x2=15．950），CAIX高表达组1、3、5、7年肿瘤特异性生存率分别为95．2％、83．9％、81．2％、78．2％，CAIX低表达组分别为89．5％、63．9％、46．8％、40．1％。2组术后肿瘤复发和（或）转移率比较差异有统计学意义（P=0．040，x2=4．200）。多因素Cox回归模型分析显示CAIX表达是影响肾透明细胞癌预后的指标（RR=0．186）。结论CAIX高表达与肾透明细胞癌患者术后死亡率及肿瘤复发和（或）转移率呈负相关，CAIX可作为判断肾透明细胞癌预后的指标。

Objective To evaluate the prognostic significance of carbonic anhydrase IX （CA IX） expression in patients with clear cell renal cell carcinoma （ecRCC）. Methods CA IX expression in a cohort of 120 patients with ccRCC was evaluated by P-V immunohistochemistry with a rabbit CA IX polyelonal antibody. Twenty-five normal kidney tissues were used as a control. 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 One hundred and twelve （93.3%） patients were followed up with the median follow-up time of 45 months （ range, 6 to 94 months）. Seventy-five patients survived without evidence of tumor recurrence, 3 patients survived with tumor recurrence, and 34 patients died, 28 of the 34 died of cancer. CA IX expression was negative in all normal renal tissue. High CA IX expression was observed in 89 （74.2%） patients, among which 82 patients were followed up, and the disease free survival was 75.6% （62/82）. Two （2.4%） patients survived with tumor recurrence, and 18 （22.0%） patients died, of which 13 （ 15.9% ） died of cancer. Tumor recurrence and （or） metastasis occurred in 9 （ 11.0% ） patients, with a median survival of 92 months in this high expression group. Low CA IX expression was observed in 31 （25.8%） patients, among which 30 patients were followed up, and the disease free survival was 43.3% （13/30）. One （3.3%） patient survived with tumor recurrence, and 16 （53.3%） patients died, of which 15 （50.0%） died of cancer. Tumor recurrence and （or） metastasis occurred in 8 （26.7%） patients with a median survival of 53 months in this low expression group. Cancer specific survival between CA IX high expression group and low expression group was significantly different （P = 0. 000, X2 = 15. 950） , and tumor relapse and （or） metastasis rates were significantly different （ P = 0. 040, X2 = 4.200）. The 1, 3, 5 and7 year cancer specific survival rates were95.2%, 83.9%, 81.2% and78.2% respectively in the high CA IX expression group, and 89.5% , 63.9% , 46.8% and 40.1% respectively in the 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 could be used as a prognostic biomarker in ccRCC.