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.