Localization of acidic fibroblast growth factor, fibroblast growth factor receptor-4, transforming growth factor-alpha, and epidermal growth factor receptor in human endocrine cells of the gut and related tumors: An immunohistochemical study

Gastrointestinal endocrine tumors (GETs) are neoplasms of uncertain etiopat hogenesis that often show a prominent fibroblast and smooth muscle cell pro liferation within the tumor stroma. Acidic fibroblast growth factor (aFGF) and transforming growth factor-alpha (TGF alpha) are potent mitogens for bo th mesenchymal and epithelial cells, and their biologic activities depend o n binding to specific receptors, including fibroblast growth factor recepto r-4 (FGFR4) and epidermal growth factor receptor (EGFR). To evaluate the ro les of these growth factors and their respective receptors in the pathogene sis of stromal lesions and tumor growth, we investigated their immunohistoc hemical expression in 43 normal gastrointestinal mucosa samples and 53 GETs . aFGF expression was found in a subgroup of enterochromaffin (EC) cells of the gastric and intestinal mucosa, whereas FGFR4 was localized only in col orectal L cells. TGF alpha was expressed in intestinal EC cells and colorec tal L cells, whereas EGFR was not detected in any gut endocrine cell. aFGF was localized in all EC-cell neoplasms and was coexpressed with FGFR4 in mo st cases. This receptor was also found in all L-cell tumors and in a few of the other types of GETs. EGFR was not detected in any of the GETs examined . Several stromal cells of GETs, including fibroblasts and smooth muscle ce lls, showed FGFR4 and EGFR immunoreactivity. Tumors expressing both aFGF an d TGF alpha presented a stroma that was more abundant than that of GETs exp ressing none or only one of these factors. These results suggest that FGFR4 expression may be involved in the development of EC-cell tumors through an autocrine mechanism, and that the abundant fibromuscular stroma may be rel ated to the concurrent production of both aFGF and TGF alpha by tumor cells .