[Show abstract][Hide abstract] ABSTRACT: Recent studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. We examined the expression of p53 and vascular endothelial growth factor (VEGF), a well-characterized angiogenic inducer, together with microvessel density to investigate the role of p53 in the regulation of angiogenesis and its clinical significance in human colorectal carcinoma. Surgically resected specimens of 163 colorectal carcinomas were studied by immunohistochemical staining for p53 protein, VEGF and factor VIII-related antigen. Positive p53 protein accumulation and VEGF expression was found in 41.7% and 49.1% of tumors, respectively. p53 and VEGF staining status was identical in 65.6% of tumors. The incidence of p53- or VEGF-positive tumors was significantly higher in patients with venous invasion and liver metastases than in those without. The microvessel count (MVC) in p53- or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53- and VEGF-positive tumors was significantly higher than that in the other subgroups. Neither synchronous nor metachronous hepatic metastases were found in patients with p53- and VEGF-negative tumors, while 52.2% of patients with both-positive 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 carcinoma. Combined analysis of p53 and VEGF expression might be useful for predicting the occurrence of liver metastasis in patients with this disease.
Full-text · Article · Nov 1997 · International Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND. Many studies have shown that angiogenesis plays an important role in the growth, progression, and metastasis of solid tumors. Recently, several angiogenic factors have been identified. Vascular endothelial growth factor (VEGF) is thought to be one such angiogenic factor and is also thought to be a selective mitogen for endothelial cells. We investigated the correlation between the expression of VEGF and the progression of gastric carcinoma. METHODS. One hundred twenty-nine specimens resected from patients with gastric carcinoma were investigated by staining with a polyclonal antibody against VEGF. Correlations between the expression of VEGF, microvessel density, and various clinicopathologic factors were studied. RESULTS. Microvessel density, determined by immunostaining for Factor VIII related antigen, was significantly higher in VEGF-positive tumors than in VEGF-negative tumors. VEGF positivity was correlated with vessel involvement, lymph node metastasis, and liver metastasis. Moreover, patients with VEGF-positive tumors had a significantly poorer prognosis than those with VEGF-negative tumors. Multivariate analysis indicated that the expression of VEGF is an independent prognostic factor in patients with gastric cancer. According to the mode of recurrence, the frequency of hepatic metastases was significantly increased among patients with VEGF-positive tumors. CONCLUSIONS. The expression of VEGF may be a good prognostic indicator for patients with gastric carcinoma and may also be useful as a predictor of the mode of recurrence in patients with gastric carcinoma. Cancer 1996;77:858-63.