Prognostic significance of angiogenesis in rectal cancer: a morphometric investigation

Neo-angiogenesis is crucial for tumor growth and metastasis and has been proposed as an independent prognostic factor for survival in patients with solid tumors. In this study the quantitative expression of angiogenesis was investigated by direct stereologic assessment of the vascular surface density in rectal carcinoma to determine the possible correlation of angiogenesis with clinicopathological factors and prognosis.

Sections from formalin-fixed paraffin-embedded tissue blocks of 29 primary rectal carcinomas were resected and immunostained for endothelial cell factor-VIII-related antigen. The vascular surface density (VSD), number of vessels per square mm (NVES), maximum NVES (NVESmax) according to the three maximum values of NVES and number of vessels in the unit area (N) were assessed by means of morphometry. The results were related to the main prognostic variables and the survival of patients.

There were no significant differences between survivors and non-survivors in terms of the angiogenesis parameters that were investigated. The overall survival rate was not significantly different for sex, age, tumor size and differentiation, extrahepatic metastasis, depth of invasion and the mode of adjuvant therapy. However, a significantly lower overall survival rate was observed in patients with liver metastatic disease (p<0.001), lymph node involvement (p=0.04) and incomplete resection (p<0.001). Multivariate analysis indicated that only the number of vessels in the unit area (HR = 1. 028, p = 0. 04), hepatic metastases (HR=14.94, p=0.007) and type of resection (HR=23.81, p=0.004) predicted overall survival.

These findings suggest that increased tumoral vascularity, consistent with previous studies, adversely affects survival in rectal cancer patients. Liver metastatic status and completeness of the surgical resection were the most powerful criteria to predict the final outcome of these patients. Thus, neo-angiogenesis is indeed an important and key step in tumorigenesis, but it may not be the single overwhelming factor that determines recurrence and metastasis in rectal carcinoma.