Immunohistochemical localization of growth factors fibroblast growth factor-1 and fibroblast growth factor-2 and receptors fibroblast growth factor receptor-2 and fibroblast growth factor receptor-3 in normal oral epithelium, epithelial dysplasias, and squamous cell carcinoma.
OBJECTIVE
Fibroblast growth factors (FGFs) and their receptors (FGFRs) have been identified in a variety of carcinomas, but there are few studies concerning their presence in oral cancers. The objective of this study was to determine whether FGF-1, FGF-2, and high affinity receptors FGFR2 and FGFR3 are present in the pathogenesis of oral epithelial dysplasias and oral squamous cell carcinoma.


METHODS
Sections from formalin-fixed, paraffin-embedded samples of oral normal mucosa (n = 14), epithelial dysplasia (n = 20), carcinoma in situ (n = 10), and squamous cell carcinoma (n = 12) were tested for cytoplasmic staining by standard in situ immunohistochemistry with antibodies for FGF-1, FGF-2, FGFR2, and FGFR3.


RESULTS
Staining for FGF-1 is decreased or lost in the development of epithelial dysplasia and carcinoma. Staining for FGF-2 showed increased intensity (although not statistically significant) in oral epithelial dysplasias and squamous cell carcinomas and showed a significant increased expression in the upper layers of dysplasias and stratum spinosum-like cells in squamous cell carcinomas. Staining for FGFR2 showed a statistically significant increase in intensity in all layers of epithelial dysplasias and squamous cell carcinomas. Staining for FGFR3 was found in the upper stratum spinosum cells of normal and dysplastic epithelium and well-differentiated squamous cells in squamous cell carcinomas, with a statistically significant increase in staining intensity in dysplastic and carcinomatous tissues.


CONCLUSIONS
The loss of FGF-1 is consistent with loss of differentiation in dysplasias and some squamous cell carcinomas. Changes in the localization of FGF-2 and FGFR2 into upper epithelial layers with increasing dysplasia suggest increased mitotic potential of high level cells. The co-localization of FGF-2 and its high affinity receptors in neoplastic tissues suggests an autocrine mechanism of influence on carcinogenesis.
Wakulich
Candice
C
University of Western Ontario, London, Ontario, Canada.
Jackson-Boeters
Linda
L
Daley
Tom D
TD
Wysocki
George P
GP
D000906:Antibodies; D019898:Autocrine Communication; D015415:Biomarkers / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D002278:Carcinoma in Situ / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002454:Cell Differentiation; D004396:Coloring Agents; D003593:Cytoplasm / Q000648:ultrastructure; D004848:Epithelium / Q000473:pathology; D016220:Fibroblast Growth Factor 1 / Q000032:analysis*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D016555:Matched-Pair Analysis; D008938:Mitosis; D009061:Mouth Mucosa / Q000166:cytology*; D009062:Mouth Neoplasms / Q000473:pathology*; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis*; D018709:Statistics, Nonparametric
D000906:Antibodies; D015415:Biomarkers; D014408:Biomarkers, Tumor; D004396:Coloring Agents; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3