Role of transforming growth factor-beta 1 in invasion and metastasis in gastric carcinoma

Purpose: Transforming growth factor-beta1 (TGF-beta 1) is a major modulator of cellular proliferation and extracellular matrix formation. We determine d the role of TGF-beta 1 in invasion and metastasis in gastric cancer. Materials and Methods: We detected TGF-beta 1 expression in primary and lym ph node metastatic lesions of gastric cancer, using an antibody and in situ hybridization. The plasma TGF-beta 1 levels in the peripheral vein and in the tumor drainage vein were assayed. Results: In the cytoplasm of cancer cells, TGF-beta 1 was immunostained in 35.9% (78 of 217) of primary gastric carcinomas, and this expression was co nfirmed by in situ hybridization. Of 59 gastric carcinomas with a TGF-beta 1-negative primary tumor, metastatic lymph nodes were positive for TGF-beta 1 staining in 32 cases (54.2%). Positive staining of TGF-beta 1 in gastric cancer tissues was closely related to serosal invasion, infiltrative growt h, and lymph node metastasis. Multivariate analysis showed that the express ion of TGF-beta 1 was an independent risk factor for serosal invasion and i nfiltrative growth of the tumor. The plasma level of TGF-beta 1 did not dif fer between TGF-beta 1-negative and -positive groups. There were also no di fferences in plasma TGF-beta 1 levels among each tumor stage, between the p eripheral and the tumor drainage veins, and between preoperative and postop erative testings. Conclusion: Transforming growth factor-beta 1 is closely related to the inv asion and metastasis of gastric cancer, and production of TGF-beta 1 in the tumor does not contribute to the total amount of TGF-beta 1 in the blood c irculation. We interpret our observations to mean that in a tumor microenvi ronment, TGF-beta 1 alters the biologic behavior of the tumor. (C) 1999 by American Society of Clinical Oncology.