Immunohistochemical study of fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor (FGF-R) in experimental squamous cell carcinomaof rat submandibular gland

Fibroblast growth factor-2 (FGF-2) is a member of the heparin-binding growt h factor family and has mitogenic activity. Immunohistochemical expression of FGF-2 and its receptor (FGFR) was evaluated in experimentally induced sq uamous cell carcinoma as well as transforming cells of rat submandibular gl and (SMG) induced by 9,10-dimethyl-1,2-benzanthracene (DMBA)/sponge implant ation. Proliferating cells detected by proliferating cell nuclear antigen ( PCNA) staining during carcinogenesis were also compared with FGF-2 and FGFR stainings. In the normal SMG, FGF-2 and FGFR were present in the excretory , striated and intercalated duct cells. Pillar and transition cells of gran ular convoluted tubule (GCT) showed FGF-2 staining. PCNA-labeled cells in n ormal SMG were rarely observed. In 2-3 weeks after carcinogen implantation, the reactions of FGF-2 and FGFR were expressed in epithelial islands, duct -like structures and affected ductal segments. PCNA-positive cells were dev eloped in these epithelial structures. In 4-8 weeks after carcinogen implan tation, squamous epithelium appeared surrounding DMBA/sponge and gradually transforming with high PCNA labeling in the basal cells and strong staining of FGF-2 and FGFR. Squamous cell carcinoma arose within about 12 weeks of the experiment. In squamous cell carcinoma, there was an intense immunohist ochemical expression of FGF-2 and FGFR. Basal and parabasal layers of the s quamous cell carcinoma showed high PCNA labeling. FGF-2-positive cells were found in the connective tissue stroma and in inflammatory cells around the proliferating duct-like structure. Coexpression of FGF-2 and FGFR was indi cated in transforming cells during carcinogenic processes and in experiment al squamous cell carcinoma of rat SMG. These findings suggested that FGF ma y play an important role for squamous metaplasia and carcinogenesis in rat SMG as an autocrine factor and FGF-positive stromal cells may also act to s timulate epithelial proliferation. (C) 1998 Elsevier Science Ltd. All right s reserved.