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

Journal article

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.

Authors: Couvelard, A; O'Toole, D; Leek, R; Turley, H; Sauvanet, A

• Publication status: Published
• Journal: Histopathology
• Volume: 46
• Issue: 6
• Pages: 668-676
• Publication date: 2005-06-01
• DOI: 10.1111/j.1365-2559.2005.02160.x
• EISSN: 1365-2559
• ISSN: 0309-0167
• Language: English
• Keywords: Immunohistochemistry; Neovascularization, Pathologic; Lymphatic Metastasis; Necrosis; Antigens, Neoplasm; Follow-Up Studies; Survival Analysis; Female; Pancreas; Basic Helix-Loop-Helix Transcription Factors; Adult; Middle Aged; Vascular Endothelial Growth Factor A; Transcription Factors; Male; Anoxia; Humans; Tumor Markers, Biological; Fibrosis; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Carbonic Anhydrases; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasm Staging; Aged