Correlation of tumor-associated macrophages with clinicopathologic factors and angiogenesis in gastric cancer.

Abstract

54 Background: Tumor associated macrophages (TAMs) are major components of tumor environment, and polarized into M1 and M2 type. M1 has been known as antitumorigenic, whereas M2 as protumorigenic. M2 have a significant role in tumor progression by promoting tumor cell invasion, migration and angiogenesis. We evaluated the M2 macrophages to investigate its importance in predicting clinical outcome or prognosis, and the relationship between M2 and angiogenesis in patients with gastric cancer. Methods: Formalin-fixed, paraffin-embedded blocks were obtained from the 88 patients with gastric cancer. CD163+ TAMs and CD105+ vessels were evaluated by immunohistochemical staining and the extent of CD163+ TAMs in tumor were divided into three groups: (A) infiltrated TAMs in cancer cell nest (nest TAMs); (B) infiltrated TAMs in tumor stroma (stroma TAMs); and (C) infiltrated TAMs along the invasive margin of a tumor (margin TAMs). Results: The increased stroma and margin TAMs (>72 and >102, respectively) were closely correlated with lymph node metastasis, TNM stage and lymphatic invasion (p<0.05 in 3 factors) and positive correlation existed between the stroma and margin TAMs (p<0.001). Disease-free survival rate analyzed using the Kaplan– Meier method was significantly lower in patient with high stroma and margin TMAs than patient with low stroma and margin TAMs (p=0.0039 and 0.0499, respectively). CD105+ vessels showed significant correlation with lymph node metastasis and lymphatic invasion.(p=0.006 and p<0.0001, respectively) Stromal, marginal and nest TAMs were positively correlated with CD105+ vessels (p=0.001). Conclusions: M2 infiltration in tumor stroma and tumor margin in gastric cancer showed relationship with aggressive phenotypes such as lymph node metastasis, TNM stage and lymphatic invasion and was correlated with angiogenesis. This study supports the view that the adverse prognostic impact of M2 involves tumor angiogenesis in gastric cancer.