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Role of Transforming Growth Factor-ß1 in Invasion and Metastasis in Gastric Carcinoma

From the Cancer Center, Department of Surgery II, and Department of Medical Informatics, Faculty of Medicine, Kyushu University; and National Kyushu Cancer Center, Fukuoka, Japan.

Address reprint requests to Yoshihiko Maehara, MD, Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.

PURPOSE: Transforming growth factor-beta1 (TGF-ß1) is a major modulator of cellular proliferation and extracellular matrix formation. We determined the role of TGF-ß1 in invasion and metastasis in gastric cancer.

MATERIALS AND METHODS: We detected TGF-ß1 expression in primary and lymph node metastatic lesions of gastric cancer, using an antibody and in situ hybridization. The plasma TGF-ß1 levels in the peripheral vein and in the tumor drainage vein were assayed.

RESULTS: In the cytoplasm of cancer cells, TGF-ß1 was immunostained in 35.9% (78 of 217) of primary gastric carcinomas, and this expression was confirmed by in situ hybridization. Of 59 gastric carcinomas with a TGF-ß1–negative primary tumor, metastatic lymph nodes were positive for TGF-ß1 staining in 32 cases (54.2%). Positive staining of TGF-ß1 in gastric cancer tissues was closely related to serosal invasion, infiltrative growth, and lymph node metastasis. Multivariate analysis showed that the expression of TGF-ß1 was an independent risk factor for serosal invasion and infiltrative growth of the tumor. The plasma level of TGF-ß1 did not differ between TGF-ß1–negative and –positive groups. There were also no differences in plasma TGF-ß1 levels among each tumor stage, between the peripheral and the tumor drainage veins, and between preoperative and postoperative testings.

CONCLUSION: Transforming growth factor-ß1 is closely related to the invasion and metastasis of gastric cancer, and production of TGF-ß1 in the tumor does not contribute to the total amount of TGF-ß1 in the blood circulation. We interpret our observations to mean that in a tumor microenvironment, TGF-ß1 alters the biologic behavior of the tumor.

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