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

BACKGROUND, Transforming growth factors beta (TGFs beta) are involved in a variety of important cellular functions, including cell growth and differen tiation, adhesion,migration, extracellular matrix formation, and immune fun ction. Moreover, it has been reported that TGFs beta are correlated with an giogenesis. However, the role of TGF-beta as an angiogenic factor in gastri c carcinoma is still unclear. METHODS. TGF-beta 1 expression was determined in 101 patients with gastric carcinoma by immunohistochemical procedures, and this expression was compar ed in the current study with both the expression of vascular endothelial gr owth factor (VEGF), which is thought to be the most potent angiogenic facto r, and microvessel density, to evaluate the effect of TGF-beta 1 on the ang iogenesis of gastric carcinoma tissues. RESULTS. TGF-beta 1 expression was detected in 23 tumors (22.8%). TGF-beta 1 expression was more frequent in differentiated than in undifferentiated g astric carcinoma. Furthermore, TGF-beta 1 expression was significantly corr elated with the depth of invasion and the stage of disease. There was a clo se correlation between TGF-beta 1 expression and VEGF expression. There was no correlation between TGF-beta 1 expression and microvessel density, wher eas VEGF expression was significantly correlated with microvessel density. With regard to prognosis, the 5-year survival rate was 55.9% for patients w ith TGF-beta 1 positive tumors and 67.0% in patients with TGF-beta 1 negati ve tumors. Accordingly, the prognosis for patients with TGF-beta 1 negative tumors was significantly better than that for patients with TGF-beta 1 pos itive tumors. Multivariate analysis indicated that lymph node metastasis, t umor size, and TGF-beta 1 expression were independent prognostic factors. CONCLUSIONS. These results suggest that TGF-beta 1 might be associated with tumor progression by indirectly stimulating angiogenesis through the up-re gulation of VEGF expression in gastric carcinoma. (C) 1999 American Cancer Society.