title: Prognostic relevance of carbonic anhydrase-IX in high-risk, early-stage cervical cancer: a Gynecologic Oncology Group study.
abstract: OBJECTIVE
  This study aimed to determine whether carbonic anhydrase-IX (CA-IX) was associated with progression-free survival (PFS) and overall survival (OS) in women with high-risk, early-stage cervical cancer treated with adjuvant pelvic radiotherapy with or without radiosensitizing chemotherapy.
  
  
  METHODS
  CA-IX expression was detected using an immunohistochemistry assay and categorized as low when <or=80% of tumor cells exhibited CA-IX staining and high when >80% tumor cells display CA-IX staining. Associations between CA-IX expression and clinical characteristics, angiogenesis marker expression, and clinical outcome were evaluated.
  
  
  RESULTS
  High CA-IX expression was observed in 35/166 (21.1%) of cases. CA-IX expression was not associated with age, race, stage, cell type, grade, positive margins, parametrial extensions, positive lymph nodes, or lymphovascular space invasion but was associated with tumor size categorized as <2 , 2-2.9 , or >or=3 cm (high expression: 4.7% vs. 23.2% vs. 32.5%, P=0.003) and cervical invasion confined to the inner two-thirds compared with the outer third of the cervix (high expression: 6.1% vs. 23.7%, P=0.028). CA-IX expression was not associated with immunohistochemical expression of p53, CD31, CD105, thrombospondin-1, or vascular endothelial growth factor-A. Women with high versus low CA-IX expression had similar PFS (P=0.053) and significantly worse OS (P=0.044). After adjusting for prognostic clinical covariates, high CA-IX expression was an independent prognostic factor for PFS (hazard ratio [HR]=2.12; 95% confidence interval [CI]=1.13-3.95; P=0.019) and OS (HR=2.41; 95% CI=1.24-4.68; P=0.009).
  
  
  CONCLUSIONS
  Tumor hypoxia measured by immunohistochemical expression of CA-IX is an independent prognostic factor for both PFS and OS in high-risk, early-stage cervical cancer.
authors.affiliation: Department of Epidemiology, University of California at Irvine, School of Medicine, Irvine, CA, USA. syliao@uci.edu
authors.forename: Shu-Yuan
authors.initials: SY
authors.lastname: Liao
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Randall
authors.forename: Chunqiao
authors.initials: C
authors.lastname: Tian
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.forename: Robert A
authors.initials: RA
authors.lastname: Burger
authors.forename: John P
authors.initials: JP
authors.lastname: Fruehauf
authors.forename: William A
authors.initials: WA
authors.lastname: Peters
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Stock
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Stanbridge
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012307:Risk Factors; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases