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Hypoxia inducible factors 1α and 2α are associated with VEGF expression and angiogenesis in gallbladder carcinomas

✍ Scribed by A. Giatromanolaki; E. Sivridis; C. Simopoulos; A. Polychronidis; K.C. Gatter; A.L. Harris; M.I. Koukourakis

Publisher
John Wiley and Sons
Year
2006
Tongue
English
Weight
235 KB
Volume
94
Category
Article
ISSN
0022-4790

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✦ Synopsis

Aims: To investigate the significance of the hypoxia inducible factors HIF-1a and HIF-2a in gallbladder adenocarcinomas and their relation to angiogenesis and to the expression of VEGF, an angiogenic factor transcriptionally regulated by HIFas. Methods: HIF-1a and 2a expression was assessed immunohistochemically in 60 patients with early gallbladder adenocarcinomas, treated with surgery alone. In addition, the vascular density (VD) and the expression of the angiogenic factors VEGF and thymidine phosphorylase (TP) were examined. The results were correlated with clinico-pathological features and prognosis. Results: Overexpression of HIF-1a and 2a was significantly associated with increased tumor angiogenesis and VEGF expression, while HIF-2a was linked with upregulation of TP. None of these factors were associated with T-stage and tumor grade. Although HIFs did not relate significantly with prognosis, patients with HIF-1/2 expression who failed to switch-on VEGF or intratumoral angiogenesis had a favorable outcome. Conclusion: Hypoxia inducible factors are upregulated in a large proportion of gallbladder adenocarcinomas, a feature strongly related to increased expression of VEGF and intensified angiogenesis.

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