Immunohistochemical Analysis of Transforming Growth Factor Beta in Gallbladder Cancer

TGF-beta is highly expressed in various cancer cells, yet its mechanism suppressing the cell cycle fails and cell proliferation accelerates, resulting in carcinogenesis. However, there are only a very few reports on animal experiments or clinical specimens with regard to the TGF-beta in gallbladder cancer. We performed immunohistochemical analysis of TGF-beta expression with regard to cell proliferation, angiogenesis, and tumor cell infiltration in clinical specimens of gallbladder cancer. TGF-beta immunoreactivity was significantly higher in advanced cancer than in early cancer. With regard to Ki-67 labeling index, there was no significant difference between early cancer and advanced one. There was no statistically significant difference of the density of pre-existing blood vessels (CD34) between TGF-beta-positive group and negative one. The density of angiogenic vessels (CD105) was significantly greater in the TGF-beta-positive group than in the negative one. Tumor-associated macrophage infiltration was significantly higher in the TGF-beta-positive group than in the negative one. No statistically significant differences in cumulative survival rate were noted between patients in the TGF-beta-positive and TGF-beta-negative groups. In conclusion, our study revealed that in patients with gallbladder cancer, expression of TGF-beta increases according to cancer progression and strongly influences angiogenesis and macrophage infiltration, which contributes to tumor proliferation, but acts weakly on cancer cells by itself.