Hypoxia and hypoxia-regulated proteins in gastric cancer: prognostic significance for clinical outcome

Full text: To examine the relationship between hypoxia level, hypoxia-inducible factor-1α (HIF-1α) expression, tumor vascularity, and clinicopathologic parameters in gastric cancer; to assess the impact of hypoxia-associated events on the prognosis of clinical outcome. High hypoxia levels were found in 29 % of pts., and low - in 71 % of pts. Strong nuclear expressions of HIF-1α were found in 7 % of pts., moderate - in 80 % of pts., and weak - in 13 % of pts. Strong microvessel densities were observed in 54 % of pts. and moderate - in 46 % of pts. It was revealed a close association between the hypoxia level in tumor assessed by 31P NMR spectroscopy and expression of HIF-1α in tumor cells (P<0.01). It was also observed the correlation of high hypoxia level with the increased rate of microvessel density in tumor tissue (P=0.02). The HIF-1α expression correlated with histological grade of tumor (P<0.05). At the same time the correlation between expression of HIF-1α and microvessel density was not statistically significant (P>0.05). Hypoxia level and microvessel density in tumor tissue correlated with clinical stage (P<0.05). High hypoxia levels positively correlated with decreased overall survival (P=0.044). For overall survival, hypoxia level and HIF-1α expression (hazard ratio, 2.10; 95 % CI, 0.67-4.67; P=0.035 and 3.45; 0.89-3.01, 0.047, respectively) were independently predictive in multivariate analysis for lymph-node negative patients; and hypoxia level (hazard ratio, 4.50; 95 % CI, 0.42-2.57; P=0.027) for lymph-node positive patients. Statistical analysis has indicated that PME/Pi ratio in tumor tissue may be used as an parameter of hypoxia level as well as independent prognostic factor of clinical outcome in patients with gastric cancer. Methodological approaches are started now to be used in the analysis of head and neck tumors treated with hyperthermia combined with radiation/chemotherapy. (author)