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Oral and Maxillofacial Pathology| Volume 93, ISSUE 5, P573-579, May 2002

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

      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

        • Jordan RCK
        • Daley TD.
        Oral squamous cell carcinoma: new insights.
        J Can Dent Assoc. 1997; 63 (51821-5): 517
        • Saranath D
        • Bhoite LT
        • Deo MG.
        Molecular lesions in human oral cancer: the Indian scene.
        Eur J Cancer. 1993; 29B: 107-112
        • Basilico C
        • Moscatelli D.
        The FGF family of growth factors and oncogenes.
        Adv Cancer Res. 1992; 59: 115-160
        • Klein S
        • Roghani M
        • Rifkin DB.
        Fibroblast growth factors as angiogenesis factors: new insights into their mechanism of action.
        in: Regulation of angiogenesis. : Birkhauser Verlag, Basel (Switzerland)1997: 159-185
        • Goldfarb M.
        Functions of fibroblast growth factors in vertebrate development.
        Cytokine Growth Factor Rev. 1996; 7: 311-325
        • Ornitz DM.
        FGFs, heparan sulfate and FGFRs: complex interactions essential for development.
        Bioessays. 2000; 22: 108-112
        • Miller DL
        • Ortega S
        • Bashayan O
        • Basch R
        • Basilico C.
        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
        • Galzie Z
        • Kinsella AR
        • Smith JA.
        Fibroblast growth factors and their receptors.
        Biochem Cell Biol. 1997; 75: 669-685
        • Ornitz DM
        • Xu J
        • Colvin JS
        • McEwan DG
        • MacArthur CA
        • Coulier F
        • et al.
        Receptor specificity of the fibroblast growth factor family.
        J Biol Chem. 1996; 271: 15292-15297
        • Neville BW
        • Damm DD
        • Allen CM
        • Bouquot JE.
        Oral and maxillofacial pathology.
        in: : WB Saunders, Philadelphia1995: 280-288 (295-304)
        • David E
        • Daley TD
        • Jackson L.
        Cochlear distribution of aFGF and FGFR3 in the adult guinea pig [abstract].
        Triologic Society, Eastern Section,, Pittsburgh, PAJanuary 28, 2000
        • So F
        • Daley TD
        • Jackson L
        • Wysocki GP.
        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
        • Colton T.
        Statistics in medicine.
        in: : Little, Brown and Co, Boston1974: 219-221
        • Moyken Y
        • Moyken Y
        • Okamoto T
        • Sato JD
        • Takada K.
        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
        • Shermirani B
        • Crowe DL.
        Head and neck squamous cell carcinoma lines produce biologically active angiogenesis factors.
        Oral Oncol. 2000; 36: 61-66
        • Schultz-Osthoff K
        • Risau W
        • Vollmer E
        • Sorg C.
        In situ detection of basic fibroblast growth factor by highly specific antibodies.
        Am J Pathol. 1990; 137: 85-92
        • Partridge M
        • Kiguwa S
        • Luqmani Y
        • Langdon JD.
        Expression of bFGF, KGF and FGF receptors on normal oral mucosa and SCC.
        Oral Oncol. 1996; 32B: 76-82
        • Grimme HU
        • Termeer CC
        • Bennett KL
        • Weiss JM
        • Schopf E
        • Aruffo A
        • et al.
        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
        • Huges CJ
        • Reed JA
        • Cabal R
        • Huvos AG
        • Albino AP
        • Schantz SP.
        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
        • Forootan SS
        • Ke Y
        • Jones AS
        • Helliwell TR.
        Basic fibroblast growth factor and angiogenesis in squamous carcinoma of the tongue.
        Oral Oncol. 2000; 36: 437-443
        • Dellacono FR
        • Spiro J
        • Eisma R
        • Kreutzer D.
        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
        • Janot F
        • El-Naggar AK
        • Morrison RS
        • Liu T-J
        • Taylor DL
        • Clayman GL.
        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
        • Petruzzelli GJ
        • Benefield J
        • Taitz AD
        • Fowler S
        • Kalkanis J
        • Scobercea S
        • et al.
        Heparin-binding growth factor(s) derived from head and neck squamous cell carcinomas induce endothelial cell proliferation.
        Head Neck. 1997; 19: 576-582
        • Riedel F
        • Gotte K
        • Bergler W
        • Rojas W
        • Hormann K.
        Expression of basic fibroblast growth factor protein and its down-regulation by interferons in head and neck cancer.
        Head Neck. 2000; 22: 183-189
        • Yamamoto N
        • Matsutani S
        • Yoshitake Y
        • Nishikawa K.
        Immunohistochemical localization of basic fibroblast growth factor in A431 human epidermoid carcinoma cells.
        Histochem J. 1991; 96: 479-485
        • Thomas GR
        • Tubb EE
        • Sessions RB
        • Cullen KJ.
        Growth factor mRNA expression in human head and neck malignant tumors.
        Arch Otolaryngol Head Neck Surg. 1993; 119: 1247-1252
        • Schultz-Hector S
        • Haghayegh S.
        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
        • Burian M
        • Quint CH
        • Neuchrist C.
        Angiogenic factors in laryngeal carcinomas: do they have prognostic relevance?.
        Acta Otolaryngol. 1999; 119: 289-292