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
- 1 March 2006
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Annals of Surgery
- Vol. 243 (3), 334-340
- https://doi.org/10.1097/01.sla.0000201452.09591.f3
Abstract
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. 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. 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). χ2 test, Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards model. 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. 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.Keywords
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