title: Carbonic anhydrase IX overexpression is associated with diminished prognosis in esophageal cancer and correlates with Her-2 expression.
abstract: BACKGROUND
  Carbonic anhydrase IX (CAIX), a transmembrane glycoprotein, seems to play a key role in the adaption of tumor cells to hypoxia. This study was designed to investigate the clinical role of CAIX and its association with Her-2 in a large cohort of adeno- (AC) and squamous cell carcinomas (SCC) of the esophagus and their metastases.
  
  
  METHODS
  Expression of CAIX and Her-2 was investigated immunohistochemically in formalin fixed, paraffin-embedded tissue from 330 esophageal cancers (182 ACS, 148 SCCs). Corresponding lymph node metastases in 137 cases, distant metastases in 34 cases, and local recurrences in 14 cases were analyzed for CAIX expression.
  
  
  RESULTS
  A total of 147 cases (44.5%) showed strong CAIX expression (AC: 46.7%; ACC: 41.9%). CAIX status of the primary tumor influenced CAIX expression in corresponding lymph node metastases (P<0.001, linear regression). High CAIX-expression was an independent prognostic factor for shorter overall and disease-free survival (P≤0.05, Cox regression). Twenty-nine ACs (15.9%) and 6 SCCs (4.1%) showed Her-2 overexpression. In AC, a significant positive correlation between the Her-2 status and CAIX expression was found (P=0.009, chi-square test).
  
  
  CONCLUSIONS
  High CAIX expression is associated with shorter survival in esophageal cancer, and the hypoxic phenotype seems to be preserved at least during formation of lymph node metastases. Inhibition of CAIX might reduce the ability of tumor cells to establish disseminated disease. In Her-2 overexpressing ACs, blocking of this tyrosine kinase, e.g., by monoclonal antibodies, might induce this effect.
authors.affiliation: Institute of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.forename: Bettina
authors.initials: B
authors.lastname: Jesch
authors.forename: Julia
authors.initials: J
authors.lastname: Friedrich
authors.forename: Martin
authors.initials: M
authors.lastname: Riegler
authors.forename: Johannes
authors.initials: J
authors.lastname: Zacherl
authors.forename: Michael
authors.initials: M
authors.lastname: Hejna
authors.forename: Fritz
authors.initials: F
authors.lastname: Wrba
authors.forename: Andrea
authors.initials: A
authors.lastname: Schultheis
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Schoppmann
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000556:secondary; D015331:Cohort Studies; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C512817:CA11 protein, human; C508053:ERBB2 protein, human