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

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)-1alpha, HIF-2alpha, carbon...

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Main Authors: Couvelard, A, O'Toole, D, Leek, R, Turley, H, Sauvanet, A, Degott, C, Ruszniewski, P, Belghiti, J, Harris, A, Gatter, K, Pezzella, F
Format: Journal article
Language:English
Published: 2005
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author Couvelard, A
O'Toole, D
Leek, R
Turley, H
Sauvanet, A
Degott, C
Ruszniewski, P
Belghiti, J
Harris, A
Gatter, K
Pezzella, F
author_facet Couvelard, A
O'Toole, D
Leek, R
Turley, H
Sauvanet, A
Degott, C
Ruszniewski, P
Belghiti, J
Harris, A
Gatter, K
Pezzella, F
author_sort Couvelard, A
collection OXFORD
description 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)-1alpha, HIF-2alpha, 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-1alpha was expressed within tumour cells in 68%, HIF-2alpha in 46%, CA9 in 78% and VEGF in 52% of the cases. Stromal expression was also noted for HIF-2alpha 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-2alpha (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.
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spelling oxford-uuid:7d3e77cf-2bed-481f-8fb3-decab56b702d2022-03-26T21:02:19ZExpression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7d3e77cf-2bed-481f-8fb3-decab56b702dEnglishSymplectic Elements at Oxford2005Couvelard, AO'Toole, DLeek, RTurley, HSauvanet, ADegott, CRuszniewski, PBelghiti, JHarris, AGatter, KPezzella, FAIMS: 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)-1alpha, HIF-2alpha, 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-1alpha was expressed within tumour cells in 68%, HIF-2alpha in 46%, CA9 in 78% and VEGF in 52% of the cases. Stromal expression was also noted for HIF-2alpha 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-2alpha (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.
spellingShingle Couvelard, A
O'Toole, D
Leek, R
Turley, H
Sauvanet, A
Degott, C
Ruszniewski, P
Belghiti, J
Harris, A
Gatter, K
Pezzella, F
Expression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas.
title Expression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas.
title_full Expression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas.
title_fullStr Expression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas.
title_full_unstemmed Expression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas.
title_short Expression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas.
title_sort expression of hypoxia inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas
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