title: Prognostic value of carbonic anhydrase IX immunohistochemical expression in renal cell carcinoma: a meta-analysis of the literature.
abstract: BACKGROUND
  Carbonic anhydrase IX (CAIX) protein has been correlated with progression and survival in patients with renal cell carcinoma (RCC). The prognostic value of CAIX in RCC however, remains inconclusive according to published works. This study aimed to analyze CAIX as a biological marker to predict RCC patient prognosis.
  
  
  METHODS
  A literature search of the PubMed and Web of Knowledge databases was performed to retrieve original studies from their inception to December of 2013. Fifteen studies, collectively including a total of 2611 patients with renal cell carcinoma, were carefully reviewed. Standard meta-analysis methods were applied to evaluate the prognostic impact of CAIX expression on patient prognosis. The hazard ratio (HR) and its 95% confidence interval (CI) were recorded for the relationship between CAIX expression and survival, and the data were analyzed using Review Manager 5.2 software and Stata software 11.0.
  
  
  RESULTS
  In patients with RCC, low CAIX expression was associated with poor disease-specific survival (HR = 1.89, 95% CI: 1.20-2.98, P = 0.006), unfavorable progression-free survival (HR = 2.62, 95% CI: 1.14-6.05, P = 0.02) and worse overall survival (HR = 2.03, 95% CI: 1.28-3.21, P = 0.002). Furthermore, low CAIX expression was significantly associated with the presence of lymph node metastases (odds ratio (OR) = 0.31, 95% CI = 0.15-0.62, P = 0.0009) and distant metastases (OR = 0.66, 95% CI = 0.46-0.96, P = 0.03) and predicted a higher tumor grade (OR = 0.41, 95% CI = 0.31-0.54, P<0.00001).
  
  
  CONCLUSIONS
  Low CAIX expression most likely indicates poor prognosis in RCC patients. Moreover, low CAIX expression was significantly associated with unfavorable clinicopathological factors. To strengthen our findings, further well-designed prospective studies should be conducted to investigate the role of CAIX expression in RCC.
authors.affiliation: Institution of Urology and Nephrology, The third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Liao
authors.affiliation: Institution of Urology and Nephrology, The third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institution of Urology and Nephrology, The third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Shulu
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Institution of Urology and Nephrology, The third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Hequn
authors.initials: H
authors.lastname: Zou
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: Samitha
authors.initials: S
authors.lastname: Fernando
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology*; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases