Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.