Immunohistochemical study of fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor (FGF-R) in experimental squamous cell carcinomaof rat submandibular gland
S. Sumitomo et al., Immunohistochemical study of fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor (FGF-R) in experimental squamous cell carcinomaof rat submandibular gland, ORAL ONCOL, 35(1), 1999, pp. 98-104
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.