Expression Pattern of the Trefoil Factor Family 1 in Gastric Adenoma and Carcinoma

ABSTRACT

PURPOSE: The trefoil factor family 1 (TFF1) has a protective effect against gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs or ethanol. In addition, a TFF1 knockout mouse model has exhibited circumferential adenomas with high-grade dysplasia, of which 30% progressed into frankly invasive carcinomas. We tried to determine whether the expression pattern of the TFF1 could be involved in the development of sporadic gastric carcinomas. MATENRIALS AND METHODS: We examined TFF1 expression in a series of 43 sporadic gastric carcinomas and 18 gastric adenomas by immunohistochemistry. RESULTS: Strong positive TFF1 staining was identified primarily in the normal gastric mucosa, mainly in the cytoplasm of the superficial and foveolar epithelium. We found TFF1 expression in 55.8% (24 out of 43) of the gastric carcinomas and in 16.7% (3 out of 18) of the gastric adenomas. Statistically, TFF1 immunoreactivity was significantly higher in diffuse-type (82.4%) than in intestinal-type (38.5%) carcinomas (p=0.0058, Fisher's exact test). CONCLUSION: Our findings provide sufficient evidence that the expression of TFF1 in gastric cancer may simply disclose gastric-type differentiation of neoplastic cells and provide further support for the existence of at least two pathways of malignant transformation of the gastric mucosa: one via intestinal metaplasia and adenomatous dysplasia, leading to glandular carcinomas with intestinal-type differentiation, and the other via hyperplastic changes or de novo changes, leading to diffuse carcinomas and to a subset of glandular carcinomas displaying gastric-type differentiation.