title: Carbonic anhydrase IX as a marker for poor prognosis in soft tissue sarcoma.
abstract: OBJECTIVE
  Hypoxia is associated with malignant progression and poor outcome in several human tumors, including soft tissue sarcoma. Recent studies have suggested that carbonic anhydrase (CA) IX is an intrinsic marker of hypoxia, and that CA IX correlates with poor prognosis in several types of carcinoma. The aim of this study was to quantify the extent of CA IX expression and to investigate whether CA IX is a marker for poor prognosis in soft tissue sarcoma patients at high risk of developing metastasis.
  
  
  METHODS
  Archival paraffin-embedded blocks were retrieved from 47 patients with deep, large, high-grade soft tissue sarcoma. Sections from two separate and representative tumor areas were immunostained for CA IX, and the CA IX-positive area fraction was quantified by image analysis, excluding areas of normal stroma and necrosis that were identified from serial H&E-stained sections. Patients were then subject to survival analysis.
  
  
  RESULTS
  CA IX-positive area fractions of viable tumor tissue varied significantly between tumors (range, 0-0.23; median, 0.004), with positive membranous CA IX staining in 66% (31 of 47) of the tumors. Patients with CA IX-positive tumors had a significantly lower disease-specific and overall survival than patients with CA IX-negative tumors (P = 0.033 and P = 0.044, respectively).
  
  
  CONCLUSIONS
  These data suggest that CA IX, a potential intrinsic marker of hypoxia, predicts for poor prognosis in patients with deep, large, high-grade soft tissue sarcoma. Larger studies are required to determine whether CA IX has independent prognostic value in this group of tumors.
authors.affiliation: Ontario Cancer Institute/Princess Margaret Hospital, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kårstein
authors.initials: K
authors.lastname: Måseide
authors.forename: Rita A
authors.initials: RA
authors.lastname: Kandel
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bell
authors.forename: Charles N
authors.initials: CN
authors.lastname: Catton
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: Jay S
authors.initials: JS
authors.lastname: Wunder
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: David
authors.initials: D
authors.lastname: Hedley
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000860:Hypoxia; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012189:Retrospective Studies; D012983:Soft Tissue Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases