title: Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer.
abstract: OBJECTIVE
  Renal cancer response to interleukin 2 (IL-2) therapy and patient survival has been correlated with tumor histology and carbonic anhydrase IX (CAIX) expression. In an effort to confirm and expand these observations, we examined CAIX expression in pathology specimens from renal cancer patients who had previously received IL-2 therapy.
  
  
  METHODS
  Paraffin-embedded tissue sections of renal cancer were immunostained with the MN-75 monoclonal antibody to CAIX and expression levels were correlated with histologic findings and clinical outcome.
  
  
  RESULTS
  Tissue specimens were obtained from 66 patients; 27 of whom (41%) had responded to IL-2-based therapy. Fifty-eight specimens were assessed as clear cell, with 56, 33, and 4 having alveolar, granular, and papillary features, respectively. Twenty-four (36%), 31 (47%), and 11 (17%) were classified into good, intermediate, and poor prognosis groups according to the Upton pathology model. Forty-one specimens (62%) had high CAIX expression. Twenty-one of 27 (78%) responding patients had high CAIX expressing tumors compared with 20 of 39 (51%) nonresponders (odds ratio, 3.3; P = 0.04). Median survival was prolonged (P = 0.04) and survival >5 years was only seen in high CAIX expressers. In patients with intermediate pathologic prognosis, all nine responders had high CAIX expression versus 11 of 22 nonresponders. A resultant group with good pathologic prognosis alone or with intermediate pathologic prognosis and high CAIX contained 26 of 27 (96%) responders compared with 18 of 39 (46%) nonresponders (odds ratio, 30; P < 0.01) and exhibited longer median survival (P < 0.01).
  
  
  CONCLUSIONS
  CAIX expression seems to be an important predictor of outcome in renal cell carcinoma patients receiving IL-2-based therapy and may enhance prognostic information obtained from pathology specimens.
authors.affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA. Matkins@bidmc.harvard.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Atkins
authors.forename: Meredith
authors.initials: M
authors.lastname: Regan
authors.forename: David
authors.initials: D
authors.lastname: McDermott
authors.forename: James
authors.initials: J
authors.lastname: Mier
authors.forename: Eric
authors.initials: E
authors.lastname: Stanbridge
authors.forename: Amanda
authors.initials: A
authors.lastname: Youmans
authors.forename: Philip
authors.initials: P
authors.lastname: Febbo
authors.forename: Melissa
authors.initials: M
authors.lastname: Upton
authors.forename: Mirna
authors.initials: M
authors.lastname: Lechpammer
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D007376:Interleukin-2; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases