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

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 Driessen  1 , Willy Landuyt, Sylvia Pastorekova, Johnny Moons, Laurence Goethals, Karin Haustermans, Philippe Nafteux, Freddy Penninckx, Karel Geboes, Toni Lerut, Nadine Ectors
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Comparative Study

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 Driessen et al. Ann Surg. 2006 Mar.

Abstract

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.

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Figures

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FIGURE 1. The prevalence of CA IX positivity in function of the localization and the type of adenocarcinomas.
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FIGURE 2. Survival analysis, using the Kaplan-Meier method, reveals that CA IX expression is associated with a poor prognosis.
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FIGURE 3. The prevalence of VEGF positivity in function of the localization and the type of adenocarcinoma.
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FIGURE 4. A diffuse-type adenocarcinoma (A, original magnification ×20) may coexpress CA IX (B, original magnification ×20) and VEGF (C, original magnification ×20), in which the blood vessels in this tumor express CD31 (D, original magnification ×20).
See this image and copyright information in PMC

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