Expression of platelet-derived endothelial cell growth factor correlates with good prognosis in patients with colorectal carcinoma

Abstract

Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that has potent chemotactic activity for endothelial cells. Although it is expressed in the majority of colorectal tumors, and some reports suggest that its high expression is related to poor prognosis, to the authors' knowledge there is yet no consensus regarding whether PD-ECGF expression is a prognostic factor. To investigate the prognostic value of PD-ECGF and its role in tumor angiogenesis, an immunohistochemical study of PD-ECGF expression and tumor vasculature was performed and their relation with the clinicopathologic factors in patients with advanced colorectal carcinoma was evaluated. Formalin fixed, paraffin embedded specimens from 86 colorectal carcinoma patients (40 cases in the muscularis propria and 46 cases in the subserosa) were immunostained for PD-ECGF and CD31 as a marker for vascular endothelial cells and expression of PD-ECGF was evaluated using an image analysis system. Patients were divided into high expression and low expression groups based on PD-ECGF expression, and were divided into high vascular grade and low vascular grade groups based on the microvessel density. Correlations between PD-ECGF expression and vascular grade and between PD-ECGF expression,vascular grade, and the clinicopathologic features of the patients were evaluated statistically. PD-ECGF expression was observed predominantly in the tumor stroma and not in tumor cells. The cells that stained strongly for PD-ECGF were confirmed to be macrophages infiltrating the interstitial tissue of the tumor. High PD-ECGF expression was found in 56 cases (65.1%) and low expression was detected in 30 cases (34.9%). Thirty-one of 86 tumors (36.0%) showed high vascular grade and 55 (64.0%) showed low vascular grade. No correlation between PD-ECGF expression and vascular grade was found, but there was an inverse correlation between PD-ECGF expression and the rate of incidence of lymph node and hematogenous metastasis. These correlations were statistically significant. Vascular grade was not found to correlate with the clinicopathologic features. Patients with high PD-ECGF expression had a lower rate of incidence of lymphatic and hematogenous metastasis, with a consequently better prognosis than patients with low PD-ECGF expression. PD-ECGF expression did not correlate with vascular grade, suggesting that PD-ECGF plays little role in tumor angiogenesis of colorectal carcinoma. Based on these data, the authors conclude that macrophages infiltrating the tumor stroma produce PD-ECGF and play important roles in the immune reaction against the tumor rather than in tumor angiogenesis.