Basic fibroblast growth factor and fibroblastic growth factor receptor-1 may contribute to head and neck paraganglioma development by an autocrine or paracrine mechanism.
Paragangliomas are hypervascular tumors arising from neural crest-derived paraganglia that are associated with the autonomic nerve system. Mutations in genes coding for subunits of mitochondrial complex II are associated with hereditary paragangliomas, and it has been suggested that these mutations result in a pseudohypoxic signal triggering tumorigenesis. Fibroblastic growth factors are hypoxia-inducible angiogenic stimuli that are involved in the angiogenesis and tumorigenesis of several neoplasms. It has been demonstrated that basic fibroblastic growth factor (bFGF) is a survival factor for cultured chief cells of the carotid body, capable of inducing proliferation. To examine the role of this growth factor in paragangliomas, we studied the immunohistochemical expression of bFGF and its high affinity receptor fibroblastic growth factor receptor 1 (FGFR1) in 7 normal carotid bodies and in 33 head and neck paragangliomas, including 2 malignant cases and their metastases. Immunohistochemical expression of bFGF and FGFR1 in tumors was confirmed by real-time polymerase chain reaction. FGFR1 was moderately present in carotid bodies, and there was strong and significantly enhanced cytoplasmatic staining of FGFR1 in all paragangliomas. Chief cells in carotid bodies and tumors showed strong cytoplasmatic staining for bFGF. The results indicate that FGFR1 and bFGF may contribute to the development of head and neck paragangliomas.
Douwes Dekker
Pieter Bas
PB
Department of Otorhinolaryngology, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
Kuipers-Dijkshoorn
Nel J
NJ
Baelde
Hans J
HJ
van der Mey
Andel G L
AG
Hogendoorn
Pancras C W
PC
Cornelisse
Cees J
CJ
D000328:Adult; D019898:Autocrine Communication / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000032:analysis* / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D019899:Paracrine Communication / Q000502:physiology; D010235:Paraganglioma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016222:Fibroblast Growth Factor 2; D051496:Receptor, Fibroblast Growth Factor, Type 1