Clinical Significance of Angiogenic Factor Expression at the Deepest Invasive Site of Advanced Colorectal Carcinoma

Tumor angiogenesis is a complicated process for which the mechanisms remain unclear. The aim of this study was to elucidate the clinical significance of several angiogenic factor expression as a predictor of the invasive/metastatic potential and of the prognosis of advanced colorectal carcinoma (CRC) in relation to their intratumoral histologic heterogeneity. One hundred fifty two patients who had undergone surgical resection for advanced CRC entered this study. PD-ECGF, VEGF, and VEGF-C were examined immunohistochemically with antibodies 1C6-203, A-20, and C-20, respectively. Tumor microvessel density (MVD) was determined immunohistochemically with anti-CD34 antibody. Expression of PD-ECGF, of VEGF, and of VEGF-C at the deepest invasive site were detected in 77 (50.7%), 62 (30.8%), and 71 (46.7%) of the 152 lesions, respectively. PD-ECGF, VEGF, and VEGF-C expression at the deepest invasive site in lesions with liver metastasis (77, 67, and 70%) was significantly higher than that in those without liver metastasis (44, 34, and 41%). In cases with curative surgery, patients with PD-ECGF, VEGF, and VEGF-C expression at the deepest invasive site had a significantly poorer prognosis than those without PD-ECGF, VEGF, and VEGF-C expression at the deepest invasive site. PD-ECGF, VEGF, and VEGF-C expression at the deepest invasive site correlated significantly with MVD. Multivariate analysis with logistic regression for 5-year survival in patients with curative surgery showed that lymph node metastasis and VEGF expression were significant risk factors. Expression of PD-ECGF, VEGF, and VEGF-C was correlated significantly with metastatic potential and prognosis in relation to MVD. Of the several angiogenic factors, VEGF expression at the deepest invasive site of tumor was the most statistically significant indicator of prognosis in advanced CRC.