Immunohistochemical detection of fibroblast growth factor receptors in normal endocrine cells and related tumors of the digestive system

Endocrine tumors (ETs) of the digestive system produce several growth facto rs including acidic and basic fibroblast growth factors (aFGF and bFGF, res pectively), which are thought to be involved in the growth of tumor cells a nd in the proliferation of tumor stromal cells. Their actions depend on bin ding to four specific receptors-FGFR1, FGFR2, FGFR3, and FGFR4-whose distri bution in normal endocrine cells and related tumors of the gastroenteropanc reatic (GEP) system has previously been examined. Formalin-fixed, paraffin- embedded normal tissues and 60 well-characterized GEP endocrine tumors were immunostained using specific antibodies directed against various GEP hormo nes, aFGF, FGFR1, FGFR2, FGFR3, and FGFR4. Acidic FGF immunoreactivity (IR) was found in gut EC cells; FGFR1 immunoreactivity in rare duodenal endocri ne cells and in pancreatic A cells; FGFR2 immunoreactivity in gastric and d uodenal G cells, pancreatic B cells, and rectal EC cells; FGFR3 immunoreact ivity in duodenal G cells; and FGFR4 immunoreactivity in rectal L cells and in pancreatic B, PP, and A cells. Immunoreactivity for at least one of the four FGFRs was found in all tumors, independently of FGFR expression in th e putative cell of origin. EC cell tumors, which were all positive for aFGF , were found to express at least three different FGFRs. FGFRs also were loc alized in the stromal cells of all the tumors examined. The tumor stroma. w as more abundant in EC cell tumors than in other types of neoplasms. The re sults suggest that aFGF-FGFR interaction may be involved in the modulation of normal endocrine cell functions and in the regulation of tumor growth an d stromal proliferation of EC cell carcinoids.