title: Fibroblast growth factor receptor 1 amplification is a common event in squamous cell carcinoma of the head and neck.
abstract: Recently, we characterized fibroblast growth factor receptor 1 amplification as a target for a rational therapy in lung squamous cell carcinoma. Patients harboring this genetic event are currently eligible for treatment with antifibroblast growth factor receptor small-molecule inhibitors in phase I clinical trials. This has the potential to significantly improve standard therapy for lung squamous cell carcinoma patients. The aim of this study was to elucidate whether fibroblast growth factor receptor 1 amplification is also a common genetic event in head and neck squamous cell carcinoma. For this purpose, we assembled a cohort of 555 patients, including 264 with metastatic disease and 147 with recurrent disease. Formalin-fixed, paraffin-embedded material of primary tumors, metastases and recurrences were assessed for fibroblast growth factor receptor 1 copy number status using fluorescence in situ hybridization. Human papilloma virus status was detected by p16 immunohistochemistry staining and PCR-ELISA. Molecular parameters were correlated with each other and with clinicopathological data. We found 15% of primary head and neck squamous cell carcinoma to display a fibroblast growth factor receptor 1 amplification. In nearly all cases, metastatic and recurrent tumor samples shared the same amplification status as the corresponding primary tumor. Fibroblast growth factor receptor 1 amplification was associated with nicotine and alcohol consumption, but was mutually exclusive with human papilloma virus infection. Amplification of the gene was associated with parameters of worse outcome. Our data identify fibroblast growth factor receptor 1 amplification as a frequent event in primary and metastatic head and neck squamous cell carcinoma and represents a potential biomarker for more aggressive disease. Fibroblast growth factor receptor 1-amplified tumors could potentially comprise a subset of head and neck squamous cell carcinoma against which targeted small-molecule inhibitors hold therapeutic efficacy.
authors.affiliation: 1] Institute of Pathology, University of Bonn, Bonn, Germany [2] Department of Prostate Cancer Research, University of Bonn, Bonn, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Göke
authors.forename: Maike
authors.initials: M
authors.lastname: Bode
authors.forename: Alina
authors.initials: A
authors.lastname: Franzen
authors.forename: Robert
authors.initials: R
authors.lastname: Kirsten
authors.forename: Diane
authors.initials: D
authors.lastname: Goltz
authors.forename: Antonia
authors.initials: A
authors.lastname: Göke
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sharma
authors.forename: Diana
authors.initials: D
authors.lastname: Boehm
authors.forename: Wenzel
authors.initials: W
authors.lastname: Vogel
authors.forename: Patrick
authors.initials: P
authors.lastname: Wagner
authors.forename: Claudia
authors.initials: C
authors.lastname: Lengerke
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Jutta
authors.initials: J
authors.lastname: Kirfel
authors.forename: Tobias
authors.initials: T
authors.lastname: Van Bremen
authors.forename: Friedrich
authors.initials: F
authors.lastname: Bootz
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Heasley
authors.forename: Andreas
authors.initials: A
authors.lastname: Schröck
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1