Expression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas.

Couvelard A, O'Toole D, Leek R, Turley H, Sauvanet A, Degott C, Ruszniewski P, Belghiti J, Harris A L, Gatter K&Pezzella F(2005)HistopathologyExpression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomasTo 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.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.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. [ABSTRACT FROM AUTHOR]