The expression of transforming growth factor-beta1 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 differentiation, adhesion, migration, extracellular matrix formation, and immune function. Moreover, it has been reported that TGFs beta are correlated with angiogenesis. However, the role of TGF-beta as an angiogenic factor in gastric carcinoma is still unclear.


METHODS
TGF-beta1 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-beta1 on the angiogenesis of gastric carcinoma tissues.


RESULTS
TGF-beta1 expression was detected in 23 tumors (22.8%). TGF-beta1 expression was more frequent in differentiated than in undifferentiated gastric carcinoma. Furthermore, TGF-beta1 expression was significantly correlated with the depth of invasion and the stage of disease. There was a close correlation between TGF-beta1 expression and VEGF expression. There was no correlation between TGF-beta1 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-beta1 positive tumors and 67.0% in patients with TGF-beta1 negative tumors. Accordingly, the prognosis for patients with TGF-beta1 negative tumors was significantly better than that for patients with TGF-beta1 positive tumors. Multivariate analysis indicated that lymph node metastasis, tumor size, and TGF-beta1 expression were independent prognostic factors.


CONCLUSIONS
These results suggest that TGF-beta1 might be associated with tumor progression by indirectly stimulating angiogenesis through the up-regulation of VEGF expression in gastric carcinoma.
Saito
H
H
First Department of Surgery, Tottori University School of Medicine, Yonago, Japan.
Tsujitani
S
S
Oka
S
S
Kondo
A
A
Ikeguchi
M
M
Maeta
M
M
Kaibara
N
N
D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016228:Endothelial Growth Factors / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D016016:Proportional Hazards Models; D013223:Statistics as Topic; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors