Abstract
Objectives. 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. Study Design. 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.
(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:573-9)
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References
- Oral squamous cell carcinoma: new insights.J Can Dent Assoc. 1997; 63 (51821-5): 517
- Molecular lesions in human oral cancer: the Indian scene.Eur J Cancer. 1993; 29B: 107-112
- The FGF family of growth factors and oncogenes.Adv Cancer Res. 1992; 59: 115-160
- Fibroblast growth factors as angiogenesis factors: new insights into their mechanism of action.in: Regulation of angiogenesis. : Birkhauser Verlag, Basel (Switzerland)1997: 159-185
- Functions of fibroblast growth factors in vertebrate development.Cytokine Growth Factor Rev. 1996; 7: 311-325
- FGFs, heparan sulfate and FGFRs: complex interactions essential for development.Bioessays. 2000; 22: 108-112
- Compensation by fibroblast growth factor 1 (FGF1) does not account for the mild phenotypic defects observed in FGF2 null mice.Mol Cell Biol. 2000; 20: 2260-2268
- Fibroblast growth factors and their receptors.Biochem Cell Biol. 1997; 75: 669-685
- Receptor specificity of the fibroblast growth factor family.J Biol Chem. 1996; 271: 15292-15297
- Oral and maxillofacial pathology.in: : WB Saunders, Philadelphia1995: 280-288 (295-304)
- Cochlear distribution of aFGF and FGFR3 in the adult guinea pig [abstract].Triologic Society, Eastern Section,, Pittsburgh, PAJanuary 28, 2000
- Immunohistochemical localization of fibroblast growth factors Fgf-1 and Fgf-2 and receptors FGFR2 and FGFR3 in the epithelium of odontogenic cysts and tumors.J Oral Pathol Med. 2001; 30: 428-433
- Statistics in medicine.in: : Little, Brown and Co, Boston1974: 219-221
- Immunocytochemical localization of fibroblast growth factor-1 (FGF-1) and FGF-2 in oral squamous cell carcinoma (SCC).Oral Pathol Med. 1994; 23: 451-456
- Head and neck squamous cell carcinoma lines produce biologically active angiogenesis factors.Oral Oncol. 2000; 36: 61-66
- In situ detection of basic fibroblast growth factor by highly specific antibodies.Am J Pathol. 1990; 137: 85-92
- Expression of bFGF, KGF and FGF receptors on normal oral mucosa and SCC.Oral Oncol. 1996; 32B: 76-82
- Co-localization of basic fibroblast growth factor and CD44 isoforms containing the variably spliced exon v3 (CD44v3) in normal skin and in epidermal skin cancers.Br J Dermatol. 1999; 141: 824-832
- Increased expression of basic fibroblast growth factor in squamous carcinogenesis of the head and neck is less prevalent following smoking cessation.Am J Surg. 1994; 168: 381-385
- Basic fibroblast growth factor and angiogenesis in squamous carcinoma of the tongue.Oral Oncol. 2000; 36: 437-443
- Expression of basic fibroblast growth factor and its receptors by head and neck squamous carcinoma tumor and vascular endothelial cells.Am J Surg. 1997; 174: 540-544
- Expression of basic fibroblast growth factor in squamous cell carcinoma of the head and neck is associated with degree of histologic differentiation.Int J Cancer. 1995; 64: 117-123
- Heparin-binding growth factor(s) derived from head and neck squamous cell carcinomas induce endothelial cell proliferation.Head Neck. 1997; 19: 576-582
- Expression of basic fibroblast growth factor protein and its down-regulation by interferons in head and neck cancer.Head Neck. 2000; 22: 183-189
- Immunohistochemical localization of basic fibroblast growth factor in A431 human epidermoid carcinoma cells.Histochem J. 1991; 96: 479-485
- Growth factor mRNA expression in human head and neck malignant tumors.Arch Otolaryngol Head Neck Surg. 1993; 119: 1247-1252
- Beta-fibroblast growth factor expression in human and murine squamous cell carcinoma and its relationship to regional endothelial cell proliferation.Cancer Res. 1993; 53: 1444-1449
- Angiogenic factors in laryngeal carcinomas: do they have prognostic relevance?.Acta Otolaryngol. 1999; 119: 289-292
Article info
Publication history
Accepted:
February 11,
2002
Received in revised form:
December 27,
2001
Received:
November 14,
2001
Footnotes
*Reprint requests: Tom Daley, DDS Department of Pathology University of Western Ontario London, Ontario Canada N6A 5C1 [email protected]
Identification
Copyright
© 2002 Mosby, Inc. Published by Elsevier Inc. All rights reserved.