Growth factor expression and proliferation kinetics in periampullary neoplasms in familial adenomatous polyposis.

Abstract

Patients with familial adenomatous polyposis develop periampullary adenomas at a high rate. However, little is known regarding the factors that control the growth, the natural history, or the malignant potential of these tumors. In this study, the authors systematically evaluated the expression of the intestinal peptide growth factor, transforming growth factor-alpha (TGF-alpha), and its corresponding receptor, epidermal growth factor-receptor (EGF-R), in 49 periampullary adenomas and 6 periampullary carcinomas from 29 patients. Tumor proliferation rates were evaluated with the MIB-1 antibody. All periampullary adenomas and carcinomas (100%) had TGF-alpha expression, whereas 63% of adenomas and 67% of carcinomas expressed EGF-R. The extent of TGF-alpha expression was greater in carcinomas compared with adenomas and increased progressively in adenomas relative to the degree of dysplasia and villous architecture of these lesions. The extent of EGF-R expression correlated only with the degree of dysplasia in adenomas. With regard to proliferation kinetics, higher MIB-1 labeling indices were observed in adenomas that were larger, more severely dysplastic, and villous. Transforming growth factor-alpha, and to a lesser extent, EGF-R expression, correlated directly with the MIB-1 labeling indices. These results support the adenoma-carcinoma sequence in the progression of malignancy in the duodenum in familial adenomatous polyposis, suggesting a possible involvement for TGF-alpha and EGF-R expression in this process.