The expression of transforming growth factor-?1 is significantly correlated with the expression of vascular endothelial growth factor and poor prognosis of patients with advanced gastric carcinoma

Abstract

Transforming growth factors β (TGFs β) are involved in a variety of important cellular functions, including cell growth and differentiation, adhesion, migration, extracellular matrix formation, and immune function. Moreover, it has been reported that TGFs β are correlated with angiogenesis. However, the role of TGF-β as an angiogenic factor in gastric carcinoma is still unclear. TGF-β1 expression was determined in 101 patients with gastric carcinoma by immunohistochemical procedures, and this expression was compared in the current study with both the expression of vascular endothelial growth factor (VEGF), which is thought to be the most potent angiogenic factor, and microvessel density, to evaluate the effect of TGF-β1 on the angiogenesis of gastric carcinoma tissues. TGF-β1 expression was detected in 23 tumors (22.8%). TGF-β1 expression was more frequent in differentiated than in undifferentiated gastric carcinoma. Furthermore, TGF-β1 expression was significantly correlated with the depth of invasion and the stage of disease. There was a close correlation between TGF-β1 expression and VEGF expression. There was no correlation between TGF-β1 expression and microvessel density, whereas VEGF expression was significantly correlated with microvessel density. With regard to prognosis, the 5-year survival rate was 55.9% for patients with TGF-β1 positive tumors and 67.0% in patients with TGF-β1 negative tumors. Accordingly, the prognosis for patients with TGF-β1 negative tumors was significantly better than that for patients with TGF-β1 positive tumors. Multivariate analysis indicated that lymph node metastasis, tumor size, and TGF-β1 expression were independent prognostic factors. These results suggest that TGF-β1 might be associated with tumor progression by indirectly stimulating angiogenesis through the up-regulation of VEGF expression in gastric carcinoma. Cancer 1999;86:1455–62. © 1999 American Cancer Society.