High tumor-infiltrating macrophage density predicts poor prognosis in patients with primary hepatocellular carcinoma after resection.

Macrophages constitute a major component of the leukocyte infiltrate of tumors and perform distinct roles in different tumor microenvironments. This study attempted to investigate the prognostic values of tumor-infiltrating macrophages in patients with hepatocellular carcinoma after resection, paying particular attention to their tissue microlocalization. The CD68(+) macrophages were assessed by immunohistochemistry in tissues from 137 patients with hepatocellular carcinoma. Prognostic value of intratumoral, marginal, and peritumoral macrophage densities was evaluated by Kaplan-Meier analysis and Cox regression. Both intratumoral and marginal macrophage densities were associated inversely with overall survival (P = .034 and .004, respectively) and disease-free survival (P = .006 and .008, respectively). In contrast, peritumoral macrophage density was associated with neither overall survival nor disease-free survival. Intratumoral macrophage density emerged as an independent prognosticator of overall survival (hazard ratio = 1.721, P = .049) and disease-free survival (hazard ratio = 2.165, P = .007). Marginal macrophage density, but not intratumoral macrophage density, was associated with vascular invasion, tumor multiplicity, and fibrous capsule formation. Our results demonstrate that high macrophage infiltration predicts poor prognosis in patients with hepatocellular carcinoma. These results, together with our previous report showing the distinct activation patterns of macrophages in different areas of tumor tissue, implies that macrophages in those areas may use different strategies to promote the tumor progression.