Hypoxia, tumour-associated macrophages, microvessel density, VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival.

Abstract

Introduction: Hypoxia is a key feature of the microenvironment of cancer cells actively participating in tumour progression. Our study was aimed to evaluate the impact of hypoxia and hypoxia-associated factors on tumour progression and survival of patients with gastric cancer. Material and methods: One hundred and five resected specimens were used. The level of tumour hypoxia was evaluated using 31P NMR spectroscopy, CD68 (tumour-associated macrophages), CD34 (microvessel density, MVD) and VEGF expression, immunohistochemistry, MMP-2 and MMP-9 activity, zymography. Statistical analysis was conducted using Pearson’s test, Kaplan–Meier survival analysis, log-rank test and Cox proportional hazards model. Results: Intratumoral hypoxia level has been signifi cantly correlated with VEGF expression, TAM number and total protease activity. The overall survival rate of patients with strong tumour hypoxia, high level of MVD, VEGF expression, TAM and MMP activity was signifi cantly lower than that of the patients without the mentioned tumour characteristics. Conclusions: The hypoxia-associated signalling that is activated in tumours promotes tumour progression through the recruitment of macrophages, remodelling of extracellular matrix and neoangiogenesis.