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Hypoxia inducible factors 1α and 2α are associated with VEGF expression and angiogenesis in gallbladder carcinomas
Author(s) -
Giatromanolaki A.,
Sivridis E.,
Simopoulos C.,
Polychronidis A.,
Gatter K.C.,
Harris A.L.,
Koukourakis M.I.
Publication year - 2006
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.20443
Subject(s) - angiogenesis , thymidine phosphorylase , medicine , hypoxia (environmental) , hypoxia inducible factors , downregulation and upregulation , vascular endothelial growth factor , gallbladder , cancer research , hif1a , neovascularization , pathology , pathological , gallbladder cancer , vegf receptors , cancer , biology , chemistry , gene , biochemistry , organic chemistry , oxygen
Aims To investigate the significance of the hypoxia inducible factors HIF‐1α and HIF‐2α in gallbladder adenocarcinomas and their relation to angiogenesis and to the expression of VEGF, an angiogenic factor transcriptionally regulated by HIFαs. Methods HIF‐1α and 2α 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‐1α and 2α was significantly associated with increased tumor angiogenesis and VEGF expression, while HIF‐2α 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. J. Surg. Oncol. 2006;94:242–247. © 2006 Wiley‐Liss, Inc.