Expression of carbonic anhydrase IX (CA IX), a hypoxia-related protein, rather than vascular-endothelial growth factor (VEGF), a pro-angiogenic factor, correlates with an extremely poor prognosis in esophageal and gastric adenocarcinomas

Ann Surg. 2006 Mar;243(3):334-40. doi: 10.1097/01.sla.0000201452.09591.f3.


Objective: To evaluate the expression of carbonic anhydrase IX (CA IX) and vascular-endothelial growth factor (VEGF) in esophageal and gastric adenocarcinomas and in turn with the histologic subtype.

Summary background data: Tumor hypoxia is an important factor in therapy resistance. A low oxygen concentration in tumors stimulates a.o. the expression of CA IX, a marker of hypoxia, and VEGF, a pro-angiogenic factor.

Methods: We evaluated the immunohistochemical expression of CA IX and VEGF on paraffin-embedded material of 154 resection specimens: 39 esophageal, 73 cardiac, and 42 distal gastric adenocarcinomas (UICC classification). The adenocarcinomas were subtyped according to the Lauren classification (intestinal- and diffuse-type).

Statistical analysis: chi test, Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards model.

Results: CA IX and VEGF expression were independent of the localization of the tumor. However, intestinal-type adenocarcinomas showed a significantly higher expression of CA IX as well as VEGF than diffuse-type tumors. VEGF expression was associated with a high microvessel density. Although survival analysis showed that CA IX expression (P = 0.008) as well as the coexpression of CA IX and VEGF (P = 0.008) correlate with a poor outcome, only CA IX expression is an independent prognostic factor for overall survival and metastasis-free survival.

Conclusion: The difference in expression of CA IX and VEGF between intestinal- and diffuse-type adenocarcinomas may possibly explain the different clinical behavior of these tumors. CA IX expression, rather than VEGF positivity in tumors, enables the identification of a subpopulation, characterized by a more aggressive behavior and a poorer prognosis.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / biosynthesis*
  • Biomarkers, Tumor / biosynthesis*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / biosynthesis*
  • Disease Progression
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / biosynthesis*


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Vascular Endothelial Growth Factor A
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases