Role of tumor-associated macrophages in the angiogenesis of well-differentiated hepatocellular carcinoma: pathological-radiological correlation.

The role of tumor-associated macrophages (TAMs) in hepatocellular carcinoma (HCC) has not been fully investigated. The aim of the present study was to clarify whether TAMs are associated with the angiogenesis of HCC during its multistep development, especially at an early stage. Forty‑three well-differentiated HCCs and 30 well- to moderately differentiated HCCs (nodule-in-nodule lesion) were used. We immunohistochemically assessed microvessel density (by CD34) and macrophage count (by CD68 or CD163). Computed tomography hepatic angiography (CTHA) was performed for 26 well-differentiated HCCs and all 30 well- to moderately differentiated HCCs. The pathological analysis of the 43 well-differentiated HCCs revealed a positive correlation between microvessel density and macrophage count (p=0.0026, r=0.4486). Based on the CTHA findings, 26 well-differentiated HCCs classified into a hyperattenuation group (n=14) and a hypo- or isoattenuation group (n=12). The microvessel density and macrophage count of the hyperattenuation group were significantly higher than those of the hypo- or isoattenuation group (p=0.0372 and p=0.0476). In the 30 well- to moderately differentiated HCCs, microvessel density of the moderately differentiated components was significantly higher than that of the well-differentiated components (p<0.0001). However, the macrophage count of the moderately differentiated component was significantly lower than that of the well-differentiated component (p<0.0001). All the moderately differentiated components showed marked hyperattenuation on CTHA. Tumor vascularity was correlated with macrophage count in the tumor when limited to well-differentiated HCCs. TAMs may have a role in promoting angiogenesis of HCC at an early stage during its multistep development.