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Annals of Oncology 15:574-580, 2004
© 2004 European Society for Medical Oncology

Original Paper

Prognostic significance of the expression of Smad4 and Smad7 in human gastric carcinomas

Received 30 August 2003; revised 26 November 2003; accepted 22 December 2003

Background:

Transforming growth factor-ß (TGF-ß) modulates the growth and function of many cells, including those with malignant transformation. Smad proteins have been identified as major components in the intracellular signaling of TGF-ß family members.

Patients and methods:

To clarify the correlations between clinicopathologic profiles and the patient’s survival, the expression of common mediator Smad (Smad4) and inhibitory Smad (Smad7) were evaluated immunohistochemically in 304 consecutive gastric carcinomas using the tissue array method.

Results:

Positive Smad4 expression was observed in 266 (87.5%) tumors and positive Smad7 expression in 98 (32.2%) tumors. The prognosis of patients with a Smad4-positive tumor was significantly better than that of the patients with a negative tumor. The survival rate was significantly higher in patients with negative Smad7 expression than those with positive Smad7 expression. In subgroup analysis according to TNM (tumour–node–metastasis) stage, both Smad4 and Smad7 showed most significant prognostic differences in stage I gastric cancer patients. Multivariate analysis indicated that tumor size, depth of invasion, lymph node metastasis and Smad7 expression were independent prognostic factors.

Conclusion:

Enhanced expression of the TGF-ß signaling inhibitor Smad7 may present one of the novel mechanisms of TGF-ß resistance in human gastric carcinomas.

Y. H. Kim1,4, H. S. Lee2,4, H.-J. Lee1, K. Hur4, W. H. Kim2,4, Y.-J. Bang3,4, S.-J. Kim5, K. U. Lee1, K. J. Choe1 and H.-K. Yang1,4,*

1 Department of Surgery, 2 Department of Pathology, 3 National Research Laboratory for Cancer Epigenetics, 4 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; 5 Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD, USA

Key words: gastric carcinoma, prognostic factor, Smad4, Smad7, transforming growth factor-ß


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