EXPRESSION OF GROWTH-FACTORS AND THEIR RECEPTORS IN ADAMANTINOMA OF LONG BONES AND THE IMPLICATION FOR ITS HISTOGENESIS

Adamantinoma of long bones is a rare bone tumour with (immuno-) histol ogical features of epithelial cells, surrounded by various amounts of osteofibrous tissue, Recent studies have indicated that cells with an epithelial phenotype are most probably the malignant element, There is still debate as to whether the fibrous part should be designated as a benign neoplastic element of a biphasic tumour or as a reactive non-n eoplastic tissue next to an epithelioid bone tumour, The expression of fibroblast growth factor type 2 (FGF-2), epidermal growth factor (EGF ), and their respective receptors FGFR-1 and EGFR, as well as the prol iferation marker Ki-67, was studied in both constituents of adamantino ma in serial sections of 25 cases by immunohistochemistry. Expression of FGF-2 and its receptor was present in both constituents of adamanti noma, but predominated in the epithelial component, Expression of EGF and its receptor was restricted to the epithelial component of adamant inoma. Comparing osteofibrous dysplasia (OFD)-like adamantinoma with c lassic epithelial cell-rich adamantinoma, the expression of FGF-2, EGF , and EGFR was more intense and in a higher percentage of cells in cla ssic adamantinoma, Proliferative activity was found nearly exclusively in the epithelial component, These data further substantiate the hypo thesis that epithelial cells constitute the proliferating tumour cell population responsible for the malignant behaviour of adamantinoma, Th e data indicate that during progression, the epithelial cells acquire expression of FGF-2, EGF, and EGFR, accompanied by a higher proliferat ive activity, Within the epithelial cell population, there exists an a utocrine pathway of growth stimulation. Furthermore, these data point to an interaction between the epithelial and fibrous components, in wh ich the epithelial cells additionally stimulate fibrous cell growth vi a a paracrine pathway involving FGF-2. (C) 1998 John Wiley & Sons, Ltd .