IL-33-expressing microvascular endothelial cells in human esophageal squamous cell carcinoma: Implications for pathological features and prognosis.

ABSTRACT

Accumulating evidence suggests that interleukin (IL)-33 plays a critical role in regulating angiogenesis and cancer progression. In this study, we characterized the pathological importance of IL-33 deployed by tumor microvascular endothelial cells (ECs) in human esophageal squamous cell carcinoma (ESCC). The expression of IL-33 in microvascular ECs in 80 cases of ESCC was examined with immunohistochemistry (IHC) and double immunofluorescence. IHC results showed that strong IL-33-immunoreactivity (IR) in microvessels, which were confirmed to be ECs by double immunofluorescence staining with IL-33/CD31 antibodies. Moreover, high proliferative activity was shown in IL-33-positive ECs, and the IL-33 functional receptor ST2 was expressed in microvascular ECs. Clinicopathological analysis revealed that IL-33-positive microvessel density (MVD) was positively correlated with node involvement in patients with ESCC. A log rank test showed a highly significant inverse correlation between the densities of IL-33-positive MVDs and overall survival rate, and patients with higher IL-33-positive MVDs tended to have a lower survival rate (both p < 0.05). Therefore, we concluded that IL-33 deployed by microvascular ECs correlates with advanced pathological features and the long-term survival rate, which provides new insights into the regulatory mechanisms of tumor angiogenesis in the tumor microenvironment and might serve as a promising target in patients with ESCC.