Gumenyuk L. Hypoxia-inducible factor (HIF-1a) and hypoxia-associated events in gastric cancer and their relation with tumor growth

Dissertation is dedicated to the study of the interrelations between HIF-1a expression, p53, microvessel density (MVD), proliferative activity of tumor cells as well infiltration of tumor-associated macrophages (TAM) in human gastric cancer and their impact on the disease outcome. HIF-1a+ tumors were determined in 93% of patients. Tumors on the I stage of disease, well-differentiated, category T1, as well as with size < 4cm were characterized by small number of HIF-1a+ cells. Expression of HIF-1a did not correlate with level of hypoxia in gastric tumor, what indicates the nonhypoxic mechanisms of this protein expression. It was determined the correlation between HIF-1a expression and p53 protein accumulation, but correlation with MVD has been seen in tumor only with moderate level of HIF-1a expression. In tumor with high level of proliferative activity it was revealed negative correlation between MVD and number of IPO-38+ cells. CK+ cells (tumor cells) were detected in lymph nodes (LN) in 24% of patients with category N0. It was evaluated that number of TAMs in tumor correlates with level of intratumoral hypoxia, HIF-1a expression as well as metastases in LN. It was revealed the unfavorable clinical outcome in patients with p53+ tumors and tumors with high number of TAMs. More high survival of patients with HIF-1а- tumors as well as tumors characterized by HIF-1a hyperexpression was observed. The number of TAMs was found to be as independent factor of unfavorable prognosis of clinical outcome.