Phuoc Nguyen Ba, Ehara Hidetoshi, Gotoh Takahiro, Nakano Masahiro, Kamei Shingo, Deguchi Takashi, Hirose Yoshinobu
Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Oncol Rep. 2008 Sep;20(3):525-30.
This study aimed to investigate whether the expression of carbonic anhydrase IX (CAIX) is associated with the expression of vascular endothelial growth factor (VEGF) and whether the co-expression of the two correlates with survival outcome in clear cell renal cell carcinoma (ccRCC). The expression of CAIX and VEGF was evaluated immunohistochemically in 122 paraffin-embedded ccRCC specimens. The clinical significance of these markers in relation to disease-specific survival (DSS) was analyzed. Patients with a low expression of CAIX had a significantly worse prognoses than those with a high expression (p=0.0005). Inversely, patients with a high expression of VEGF had a significantly worse prognoses than the patients with a low expression (p=0.0030). Furthermore, CAIX expression significantly stratified the DSS of patients with high-stage (p=0.0001), high-grade (p=0.0392), low-grade (p=0.0273), metastasis (p=0.0034), no metastasis (p=0.0303) and ECOG-PS=0 (p=0.0003). VEGF expression significantly predicted the survival of patients with low-grade (p=0.0003), high-stage (p=0.0401) and ECOG-PS=0 (p=0.0063). A multivariate Cox regression analysis showed that tumor stage (p=0.0054), metastasis (p=0.0193), ECOG-PS (p=0.0065) and CAIX expression (p=0.0001) were independent prognostic factors of DSS. Since CAIX and VEGF expression correlated inversely (p=0.0032), the prognostic value of the co-expression of CAIX-VEGF was evaluated. Multivariate analysis revealed that the co-expression was an independent prognostic factor of DSS (p=0.0002). In addition, the co-expression was able to stratify DSS into three risk groups: high-risk, intermediate-risk and low-risk (p<0.0001). In patients with ccRCC, CAIX and VEGF expression correlated inversely. Independent expression of CAIX and a co-expression of CAIX-VEGF were found to be independent predictors of DSS. Furthermore, the co-expression data for CAIX-VEGF provide more accurate prognostic information than the individual data. This information may be useful for survival prediction and risk stratification of patients with ccRCC.
本研究旨在探讨碳酸酐酶IX（CAIX）的表达是否与血管内皮生长因子（VEGF）的表达相关，以及这两种蛋白的共表达是否与透明细胞肾细胞癌（ccRCC）的生存结果相关。采用免疫组织化学方法评估122例ccRCC石蜡包埋标本中CAIX和VEGF的表达。分析这些标志物与疾病特异性生存（DSS）相关的临床意义。CAIX低表达患者的预后明显差于高表达患者（p=0.0005）。相反，VEGF高表达患者的预后明显差于低表达患者（p=0.0030）。此外，CAIX表达显著地将高分期（p=0.0001）、高分级（p=0.0392）、低分级（p=0.0273）、转移（p=0.0034）、无转移（p=0.0303）及ECOG-PS=0（p=0.0003）患者的DSS进行分层。VEGF表达显著地预测了低分级（p=0.0003）、高分期（p=0.0401）及ECOG-PS=0（p=0.0063）患者的生存情况。多因素Cox回归分析显示，肿瘤分期（p=0.0054）、转移（p=0.0193）、ECOG-PS（p=0.0065）及CAIX表达（p=0.0001）是DSS的独立预后因素。由于CAIX与VEGF表达呈负相关（p=0.0032），因此评估了CAIX-VEGF共表达的预后价值。多因素分析显示，共表达是DSS的独立预后因素（p=0.0002）。此外，共表达能够将DSS分为三个风险组：高风险、中风险和低风险（p<0.0001）。在ccRCC患者中，CAIX与VEGF表达呈负相关。发现CAIX的独立表达及CAIX-VEGF的共表达是DSS的独立预测因素。此外，CAIX-VEGF的共表达数据比单个数据提供更准确的预后信息。该信息可能有助于ccRCC患者的生存预测和风险分层。
