Interrelationship of platelet-derived endothelial cell growth factor, liver macrophages, and tumor microvessel density in patients with cholangiocellular carcinoma.

BACKGROUND/AIMS: Microvessel density (MVD) has been studied extensively as the only factor reflecting angiogenesis and a prognostic factor in various malignant tumors. Macrophages and platelet-derived endothelial cell growth factor (PD-ECGF) also play important roles in regulating angiogenesis. The present study was conducted to examine the interrelationship of MVD, liver macrophages and PD-ECGF-positive cells in patients with cholangiocellular carcinoma.

METHODOLOGY

Thirty-one patients underwent resection of cholangiocellular carcinoma, and samples of the tumors were immunostained with CD34 antibody to evaluate the relationship between MVD and prognosis. Double immunohistochemical labeling for CD68 and PD-ECGF-positive cells was performed and classified as grade 0, grade 1, or grade 2 according to the number of double-positive cells. We also evaluated the relationship between the double-positive cell grading and prognosis or MVD, and furthermore the relationship between cancer cell PD-ECGF immunoreactivity and prognosis or MVD.

RESULTS

Univariate analysis showed that patients with a median MVD exceeding 48/field had asignificantly poorer prognosis (p=0.02). The survival rate of grade 2 patients was significantly worse than that of the other two groups (p=0.011, p=0.0001), and the survival rate of grade 1 patients was significantly worse than that of grade 0 patients (p=0.007). MVD differed significantly among the three grades (p=0.0007, Kruskal-Wallis test), and there was a significant positive correlation between MVD and grade (p=0.0001). No correlation was observed between MVD and the number of cells positive for PD-ECGF alone (p=0.42). Neither the survival rate nor MVD of PD-ECGF (+) patients differed significantly from that of PD-ECGF (-) patients (p=0.08, p=0.6).

CONCLUSIONS

Although the present results are based on a small number of patients, they suggest that liver macrophages at the invasive margin of cholangiocellular carcinoma might contribute to tumor angiogenesis through PD-ECGF secretion, and thus influence the prognosis of patients.