TUMOR ANGIOGENESIS AS A PROGNOSTIC PREDICTOR IN COLORECTAL-CARCINOMA WITH SPECIAL REFERENCE TO MODE OF METASTASIS AND RECURRENCE

Tumor angiogenesis has proved to be a useful prognostic determinant fo r patients with various solid tumors. In this study, we investigated t he quantitative expression of angiogenesis in colorectal carcinoma to determine how angiogenesis correlates with clinicopathologic factors a nd prognosis. One hundred twenty-seven specimens resected from patient s with primary colorectal carcinoma were investigated immunohistochemi cally using a polyclonal antibody against factor-VIII-related antigen, and areas with the highest vascular density at the invasive tumor mar gin were counted at 200 times magnification. The microvessel count, de fined as angiogenesis density (AD), became significantly higher with i ncrease in histologic grade (p = 0.02) and Dukes stage (p = 0.001). AD was also significantly higher in patients with lymph node metastasis (p = 0.005), lymphatic invasion (p = 0.042), vascular invasion (p < 0. 001), and liver metastasis (p = 0.0004) than in those without. In addi tion, patients with synchronous distant hematogenous metastasis in sta ge D disease showed significantly higher AD than patients with nonhema togenous metastasis (p = 0.006). When 27 cases of disease recurrence a fter surgical resection with curative intent were stratified according to mode of spread, AD in cases with a hematogenous pattern of relapse proved to be significantly higher than in cases with nonhematogenous spread (p < 0.001). No significant differences were, however, found in AD when they were subdivided as to operative nodal status (p = 0.39 a nd 0.08 in the node-negative and the node-positive group, respectively ). Multivariate analysis indicated that AD was an independent prognost ic factor (p = 0.0004) in colorectal carcinoma. Quantitative evaluatio n of tumor angiogenesis at the invasive tumor margin is suggested to b e a good prognostic indicator and a useful predictor for hematogenous spread and recurrence in patients with colorectal carcinoma.