Polarized CD163+ tumor-associated macrophages are associated with increased angiogenesis and CXCL12 expression in gastric cancer

Abstract

Tumor-associated macrophages (TAMs) play a significant role in tumor progression and angiogenesis. However, the prognostic value of TAMs in different histologic locations of gastric cancer (GC) is still unknown. We evaluated the distribution of TAMs in different histologic locations to investigate its importance in predicting prognosis and the relationship with angiogenesis and CXCL12 expression in GC. The distribution of TAMs and microvessel density (MVD) in 113 GC samples were evaluated by immunohistochemical staining of CD163 and CD105, respectively. The extent of TAM distribution in the tumor was categorized into three groups: infiltrated TAMs in the tumor nest (TN), tumor stroma (TS) and invasive tumor margin (TM). The expression of CXCL12 in GC were evaluated by immunohistochemical staining of tissues from 88 GC samples. The increased CD163+ TAMs in TS and TM were closely correlated with tumor size, depth of invasion, TNM stage, lymph node metastasis, and lymphovascular invasion. TAMs in TN was not related with any clinicopathologic characteristics except histologic differentiation. The high infiltration of CD163+ TAMs in TS and TM were significantly correlated with poor overall survival. Regardless of location, CD163+ TAMs were significantly correlated with increased MVD. CXCL12 expression was significantly associated with increased CD163+ TAMs in TS and TM. TAMs in different histologic locations in GC were related to distinct aspects of tumor progression. CD163+ TAMs in TS and TM are associated with tumor progression and CXCL12 expression in GC. TAMs may be involved in tumor progression through the angiogenesis.