Overexpression of Tie2 is associated with poor prognosis in patients with gastric cancer

Abstract

Tunica Interna endothelial cell kinase (Tie2)-expressing macrophages (TEMs) are a subgroup of tumor-associated macrophages that are associated with a poor prognosis in numerous types of cancer. The present study aimed to assess the prognostic impact of Tie2 expression in gastric cancer tissues. Between January 2009 and December 2009, 76 newly diagnosed patients with gastric cancer at the Southwest Hospital, Third Military Medical University (Chongqing, China) were enrolled. TEMs were detected using immunohistochemistry. Tie2, cluster of differentiation (CD)68 and carbonic anhydrase IX (CAIX) were analyzed using immunohistochemistry and immuno-fluorescent microscopy. Tie2 protein expression was analyzed using western blot analysis in hypoxic and normoxic gastric cancer tissues. The number of TEMs positively staining for Tie2 increased with the tumor-node-metastasis (TNM) stage: 0, 53.9, 75.6 and 100% in stages I, II, III and IV, respectively (P<0.001). Tumor size and lymph node involvement were significantly associated with the presence of Tie2 in the tumor stroma (P<0.001). There was no significant difference between Tie2 and CAIX, irrespective of how the patients were grouped (tumor size, lymph node involvement, TNM stage or histological grade). Tie2 protein expression was increased in the hypoxic regions of gastric tumors.Tie2 and CD68 expression colocalized in hypoxic and normoxic gastric cancer tissues. The 1-, 2- and 3-year recurrence rates of the TEM-positive group were 31.4, 56.9 and 66.7%, respectively, as compared with 8, 28 and 48%, respectively, for the TEM-negative group (P<0.05). In the TEM-negative group, 2 patients succumbed to the disease, as compared with 21 patients in the TEM-positive group (P<0.05). Therefore, high quantities of TEMs, represented by Tie2 expression, in gastric tumors may be associated with poor survival.