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Expression of hypoxia‐inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas
Author(s) -
Couvelard A,
O'Toole D,
Leek R,
Turley H,
Sauvanet A,
Degott C,
Ruszniewski P,
Belghiti J,
Harris A L,
Gatter K,
Pezzella F
Publication year - 2005
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2005.02160.x
Subject(s) - angiogenesis , stromal cell , hypoxia (environmental) , pathology , hypoxia inducible factors , vascular endothelial growth factor , immunohistochemistry , neovascularization , biology , cancer research , hif1a , medicine , vegf receptors , chemistry , gene , organic chemistry , oxygen , biochemistry
Aims: To study the expression of hypoxia‐regulated markers in pancreatic ductal adenocarcinomas (PA) in relationship to the presence of a fibrotic focus, angiogenesis quantification and clinical outcome. Methods and results: The expression of hypoxia‐inducible factor (HIF)‐1α, HIF‐2α, carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) was immunohistochemically detected in 50 PA and correlated with tumour characteristics, microvascular density (MVD) and survival. HIF‐1α was expressed within tumour cells in 68%, HIF‐2α in 46%, CA9 in 78% and VEGF in 52% of the cases. Stromal expression was also noted for HIF‐2α and CA9 in, respectively, 42% and 48% of the cases. Tumour CA9 expression was associated with that of VEGF ( P = 0.004) and that of stromal HIF‐2α ( P = 0.013), with the presence of a fibrotic focus ( P = 0.046) and with an increased MVD ( P = 0.034). Tumour VEGF expression correlated with the presence of a fibrotic focus ( P = 0.039) and a greater MVD ( P = 0.047). Both the presence of a fibrotic focus ( P = 0.0002) and high tumour CA9 expression ( P = 0.029) were associated with reduced overall survival. Conclusion: The strong association of the presence of a fibrotic focus with CA9 expression and lower survival demonstrates that hypoxia‐driven angiogenesis plays an important role in the progression of PA.