COMBINED ANALYSIS OF P53 AND VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION IN COLORECTAL-CARCINOMA FOR DETERMINATION OF TUMOR VASCULARITY AND LIVER METASTASIS

Recent studies have demonstrated that the p53 tumor suppressor gene pl ays an important role in controlling tumor angiogenesis. We examined t he expression of p53 and vascular endothelial growth factor (VEGF), a well-characterized angiogenic inducer, together with microvessel densi ty to investigate the role of p53 in the regulation of angiogenesis an d its clinical significance in human colorectal carcinoma. Surgically resected specimens of 163 colorectal carcinomas were studied by immuno histochemical staining for p53 protein, VEGF and factor VIII-related a ntigen. Positive p53 protein accumulation and VEGF expression was foun d in 41.7% and 49.1% of tumors, respectively. p53 and VEGF staining st atus was identical in 65.6% of tumors. The incidence of p53- or VEGF-p ositive tumors was significantly higher in patients with venous invasi on and liver metastases than in those without. The microvessel count ( MVC) in p53- or VEGF-positive tumors was significantly higher than tha t in negative tumors, and MVC in both p53- and VECF-positive tumors wa s significantly higher than that in the other subgroups, Neither synch ronous nor metachronous hepatic metastases were found in patients with p53- and VEGF-negative tumors, while 52.2% of patients with both-posi tive tumors had liver metastases and had a poorer prognosis than those with both-negative tumors, Our findings suggest the presence of a p53 -VEGF pathway regulating tumor angiogenesis in human colorectal carcin oma. Combined analysis of p53 and VEGF expression might be useful for predicting the occurrence of liver metastasis in patients with this di sease. (C) 1997 Wiley-Liss, Inc.