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.

Summary It is known that angiogenesis plays an important role in the growth and metastasis of solid tumours. Several angiogenic factors have been identified and platelet-derived endothelial cell growth factor (PD-ECGF) is thought to be one such factor. Recently, it was reported that thymidine phosphorylase (dThdPase) is identical to PD-ECGF. Using immunohistochemical staining with an anti-dThdPase antibody, we investigated the correlation between dThdPase expression and the microvessel density in 120 gastric carcinomas. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in dThdPase-positive tumours than in dThdPase-negative tumours. There was a significant correlation between dThdPase expression and the increment of microvessel density. Moreover, regarding distant organ metastasis, the frequency of hepatic metastasis was significantly higher (P<0.01) in patients with dThdPase-positive tumours than in those with dThdPase-negative tumours. In summary, it was suggested that dThdPase expression is closely associated with the promotion of angiogenesis and hepatic metastasis in gastric carcinoma.

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Recently, it has been reported that p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis by regulating expression of vascular endothelial growth factor (VEGF), which is a well-characterized angiogenic inducer. In this study, we investigated these antigens’ expression together with microvessel density, and investigated their clinical importance. One hundred twenty specimens resected from patients with gastric carcinoma were investigated using immunohistochemical methods. p53 and VEGF expression was observed in 42 and 35% tumors, respectively. p53 and VEGF staining status was coincided in 72% tumors, and a significant correlation was found between p53 and VEGF status. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in p53-positive or VEGF-positive tumors. According to prognosis, patients with p53-positive tumors had significantly worse survival than those with p53-negative tumors. There was also a significant worse survival in the patients with VEGF-positive tumors than those with VEGF-negative tumors. Moreover, the 5-year survival rate was lowest in the patients with p53-positive and VEGF-positive tumors, while it was highest in the patients with p53-negative and VEGF-negative tumors. In conclusion, both p53 and VEGF significantly correlated with tumor vascularity and prognosis in patients with gastric carcinoma.

BACKGROUND Recently many studies have demonstrated that the degree of tumor angiogenesis is related to the aggressiveness of the tumor and clinical outcome. Vascular endothelial growth factor (VEGF) is a well characterized inducer of angiogenesis. In this study, the authors investigated the prognostic significance of VEGF expression in patients with early gastric carcinoma together with p53 gene abnormality and tumor cell proliferation. METHODS One hundred ninety‐five endoscopically biopsied specimens obtained preoperatively from patients with early gastric carcinoma were studied immunohistochemically. RESULTS According to conventional clinicopathologic factors, submucosal invasion, lymph node metastases, and tumor size were associated significantly with the incidence of disease recurrence. According to conventional biologic factors, VEGF expression was observed more frequently in patients with disease recurrence compared with those without disease recurrence whereas neither p53 abnormality nor tumor cell proliferation were correlated with prognosis. Moreover, multivariate analysis indicated that VEGF expression (as well as submucosal invasion and lymph node metastases) is an independent predictor of disease recurrence. CONCLUSIONS The results of the current study show that VEGF expression may be a useful prognostic factor for patients with early gastric carcinoma. Cancer 1999;86:566–71. © 1999 American Cancer Society.

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.

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.