Overexpression of HIF-1α and high density of tumor associated macrophages predict tumor aggression, invasion and unfavorable prognosis of Kazakh esophageal squamous cell carcinomas

Background: A hypoxic tumor microenvironment promotes the recruitment and transformation of macrophages and facilitates tumor progression. Hypoxia-induced factor-1α (HIF-1α) is a key factor in hypoxia. It is not clear whether HIF-1α and tumor associated macrophages (TAMs) play a synergistic role in neoplastic progression. Here we investigated potential synergism between HIF-1α and TAMs in the progression of Kazakh esophageal squamous cell carcinoma (ESCC). Methods We used immunohistochemistry (IHC) verify the expression of HIF-1α and vascular endothelial growth factor (VEGF) in tumor tissue. CD163 was used as a marker for TAMs, and the density of TAMs in tumor tissues were determined. Kazakh ESCC samples exhibited higher expression of HIF-1α and VEGF and greater density of TAMs compared to cancer adjacent normal (CAN) tissues. Results Overexpression of HIF-1α was significantly correlated with vascular invasion, lymph node metastasis and the clinical tumor stage of Kazakh ESCCs. Overexpression of HIF-1α was also associated with poor prognosis of Kazakh ESCC. Moreover, overexpression of HIF-1α was positively correlated with high TAM density and overexpression of VEGF ( P  < 0.05). Furthermore, the correlation between VEGF overexpression and high density of TAMs was very significant ( P  < 0.001). Conclusions These data suggest that overexpression of HIF-1α may increase the infiltration of TAMs in Kazakh ESCC, thereby increasing VEGF expression, which may in turn promote the progression of Kazakh ESCC.