title: Prognostic value of the co-expression of carbonic anhydrase IX and vascular endothelial growth factor in patients with clear cell renal cell carcinoma.
abstract: 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.
authors.affiliation: Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Nguyen Ba
authors.initials: NB
authors.lastname: Phuoc
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Ehara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Gotoh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakano
authors.forename: Shingo
authors.initials: S
authors.lastname: Kamei
authors.forename: Takashi
authors.initials: T
authors.lastname: Deguchi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Hirose
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000556:secondary; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases