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.

Multiple genetic changes occur during the evolution of normal cells into cancer cells. It has been reported that both cyclin D1 and p53 genes play major roles in oncogenesis and/or cell cycle control in various cancers. In this study, we examined the overexpression of cyclin D1 and p53 by the immunohistochemical method and investigated the correlation between expression of these antigen and prognosis in patients with colorectal adenocarcinoma. Disease-free survival was significantly lower in the patients with cyclin D1-strongly positive tumors than in those with cyclin D1-negative tumors. Similarly, disease-free survival of the patients with p53-strongly positive tumors was significantly lower than that of those with p53-negative tumors. Moreover, multivariate analysis indicated that both cyclin D1 and p53 overexpression are independent prognostic factors in patients with colorectal adenocarcinoma. In conclusion, both cyclin D1 and p53 overexpression may be useful predictors of disease recurrence in patients with colorectal adenocarcinoma.

Background: The aim of this study was to determine a predictive indicator of gemcitabine (GEM) efficacy in unresectable pancreatic cancer using tissue obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA).

Recently, it has been reported that cyclin D₁ plays a major role in oncogenesis in various cancers; however, there have been few studies on the association of cyclin D₁ overexpression and prognosis of patients with malignant tumors. We evaluated the prognostic significance of cyclin D₁ overexpression in colorectal adenocarcinoma. One hundred twenty-three specimens resected from patients with colorectal adenocarcinomas were investigated by staining with a monoclonal antibody against cyclin D₁. As a result, both overall survival and disease-free survival were significantly poorer in the patients with tumors strongly positive for cyclin D₁ than in those with cyclin-D₁-negative or weakly positive tumors. The 5-year survival rate of the patients with tumors strongly positive for cyclin D₁ was 53.3%, while the 5-year survival rates of patients with cyclin-D₁-negative and weakly positive tumors were 96.2 and 78.8%, respectively. Moreover, multivariate analysis indicated that cyclin D₁ overexpression is an independent predictor of disease recurrence in our patients. In conclusion, cyclin D₁ overexpression may be useful as a predictor of disease recurrence in colorectal adenocarcinoma.

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