Combined analysis of p53 and vascular endothelial growth factor expression in colorectal carcinoma for determination of tumor vascularity and liver metastasis

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. Int. J. Cancer 74:502–507, 1997. © 1997 Wiley‐Liss, Inc.

Growth dysregulation and p53 accumulation in human primary colorectal cancer

“…In established cancers, p53 inactivation is commonly associated with intracellular p53 protein accumulation (Hall and Lane, 1994). The present study has shown p53 accumulation in 59% of colorectal tumours, in accord with previous findings (Kang et al, 1997;Ahnen et al, 1998).…”

“…Functional inactivation of p53 promotes genomic instability (Bischoff et al, 1990) and is commonly, though not universally, associated with intracellular p53 protein accumulation (Hall and Lane, 1994;Save et al, 1998). p53 accumulation is detectable in many colorectal cancers (Purdie et al, 1991;Scott et al, 1991), with 40-60% having immunologically detectable levels (Kang et al, 1997;Ahnen et al, 1998). However, effects on growth homeostasis are unclear.…”

Lymphatic microvessel density as prognostic marker in colorectal cancer

“…5,[43][44][45][46][47] Some studies have indicated that VEGF expression is an independent prognostic factor in predicting patient prognosis, 5,[43][44][45] while others have reported no such association. 46 Chung et al 47 also showed that VEGF expression was significantly associated with prognosis and hematogenous spread in colorectal carcinoma.…”

An analysis of p53, BAX and vascular endothelial growth factor expression in node-positive rectal cancer. Relationships with tumour recurrence and event-free survival of patients treated with adjuvant chemoradiation

“…Neovascularization sustained by VEGF up-regulation is necessary for tumour nourishment and it is a potential route for haematogenous spread and metastasis. Previous data contribute to support this hypothesis; high VEGF protein expression or mRNA levels correlated with the M1 stage and liver metastases from colorectal carcinomas (Kang et al, 1997;Tokunaga et al, 1998;Lee et al, 2000).…”