# M2 Tumor-Associated Macrophages and Microvessel Density at the Invasive Front of Resected Gastric Adenocarcinoma: A Clinicopathological Study

## TL;DR

This study examines how M2 macrophages and blood vessel density at the edge of gastric tumors relate to cancer progression and survival.

## Contribution

The study identifies microvessel density as an independent favorable prognostic marker in gastric cancer.

## Key findings

- Higher M2 macrophage counts correlate with increased angiogenesis and deeper tumor invasion.
- Increased microvessel density is independently associated with better overall survival.
- The tumor invasive front shows biologically significant interactions between macrophages and blood vessels.

## Abstract

Gastric cancer is associated with poor survival, and improved understanding of the tumor microenvironment may help refine prognosis and guide future therapies. Among immune cells, tumor-associated macrophages (TAMs) play an important role, particularly M2-polarized macrophages, which promote tumor growth, invasion, and angiogenesis. In this study, we analyzed tissue samples from 106 patients who underwent radical R0 surgery for gastric cancer. We focused on the tumor invasive front and assessed the number of M2 macrophages (CD163+) and microvessel density (MVD). Higher numbers of M2 macrophages were associated with increased angiogenesis and deeper tumor invasion. Although M2 macrophages were not independent predictors of survival, higher microvessel density was independently associated with better overall survival. These findings suggest that the tumor invasive front is a biologically distinct region where interactions between macrophages and blood vessels influence tumor behavior and may have prognostic relevance in gastric cancer.

Background/Objectives: Gastric cancer (GC) remains a major cause of cancer-related deaths worldwide. The tumor microenvironment, particularly tumor-associated macrophages (TAMs), plays a key role in tumor progression and angiogenesis. M2-polarized TAMs are considered pro-tumorigenic; however, their prognostic significance and relationship with microvessel density (MVD) at the invasive front of GC remain unclear. This study evaluated the prognostic significance of CD163+ M2 TAMs and MVD at the invasive front of gastric adenocarcinoma. Methods: A retrospective analysis was performed on 106 patients who underwent radical R0 surgery for GC without neoadjuvant therapy. Immunohistochemistry using CD163 and CD34 antibodies was applied to quantify M2 TAMs and MVD at the invasive front. Median values were used as cut-offs. Associations with clinicopathological features were analyzed, and survival was assessed using Kaplan–Meier and Cox regression models. Results: The mean number of CD163+ M2 TAMs was 70, and the mean MVD was 33. A significant positive correlation between M2 TAMs and MVD was observed (p = 0.001). Higher M2 TAMs infiltration was associated with deeper tumor invasion (pT) and showed a trend toward advanced pTNM stage. In univariate analysis, neither M2 TAMs nor MVD was associated with survival. Multivariate analysis identified pT (p = 0.02) and MVD (p = 0.03) as independent prognostic factors, with increased MVD associated with improved overall survival. Conclusions: CD163+ M2 TAMs are linked to angiogenesis at the invasive front of gastric cancer and correlate with tumor invasiveness. Increased MVD may represent an independent favorable prognostic marker, highlighting the biological importance of the invasive tumor front.