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Prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell carcinomas of the head and neck

  • Original Article – Cancer Research
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Abstract

Background

FGFR1 is a receptor tyrosine kinases involved in tumor growth signaling, survival, and differentiation in many solid cancer types. There is growing evidence that FGFR1 amplification might predict therapy response to FGFR1 inhibitors in squamous cell lung cancers. To estimate the potential applicability of anti FGFR1 therapies in squamous cell carcinomas of the head and neck, we studied patterns of FGFR1 amplification using fluorescence in situ hybridization (FISH).

Materials and methods

A tissue microarray was constructed from 453 primary treatment-naive squamous cell carcinomas of the head and neck regions with histopathological and clinical follow-up data [including oral cavity (n = 222), oropharynx (n = 126), and larynx (n = 105)]. FGFR1 and centromere 8 copy numbers were assessed by dual-color FISH. FGFR1 amplification was defined as a copy number ratio FGFR1: centromere 8 ≥ 2.0. HPV sequencing and p16 immunohistochemistry (IHC) were applied to FGFR1-amplified cancers.

Results

FISH analysis was successful in 297 (66%) of the 453 cancers. FGFR1 amplification was found in 6% of analyzable tumors, and was more frequent in tumors of the oral cavity (13/133 amplified, 10%), than cancers of other localizations (1/79 oropharynx, 4/85 larynx; p = 0.007 and 0.159, respectively). One out of 18 FGFR1 amplified cancers was HPV positive. No associations were found between FGFR1 amplification and tumor phenotype or p16 IHC.

Conclusions

Head and neck cancers are recurrently affected by FGFR1 amplification, with a predominance in cancers of the oral cavity. Finding only one HPV positive and FGFR1 amplified cancer argues against a causal relationship between HPV and FGFR1 amplifications.

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References

  • Andre F, Bachelot T, Campone M, Dalenc F, Perez-Garcia JM, Hurvitz SA, Turner N, Rugo H, Smith JW, Deudon S, Shi M, Zhang Y, Kay A, Porta DG, Yovine A, Baselga J (2013) Targeting FGFR with dovitinib (TKI258): preclinical and clinical data in breast cancer. Clin Cancer Res 19:3693–3702. doi:10.1158/1078-0432.CCR-13-0190

    Article  CAS  PubMed  Google Scholar 

  • Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578. doi:10.1056/NEJMoa053422

    Article  CAS  PubMed  Google Scholar 

  • Bousquet G, Alexandre J, Le Tourneau C, Goldwasser F, Faivre S, de Mont-Serrat H, Kaiser R, Misset JL, Raymond E (2011) Phase I study of BIBF 1120 with docetaxel and prednisone in metastatic chemo-naive hormone-refractory prostate cancer patients. Br J Cancer 105:1640–1645. doi:10.1038/bjc.2011.440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA (2005) Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 23:8646–8654. doi:10.1200/JCO.2005.02.4646

    Article  PubMed  Google Scholar 

  • Castellsague X, Quintana MJ, Martinez MC, Nieto A, Sanchez MJ, Juan A, Monner A, Carrera M, Agudo A, Quer M, Munoz N, Herrero R, Franceschi S, Bosch FX (2004) The role of type of tobacco and type of alcoholic beverage in oral carcinogenesis. Int J Cancer 108:741–749. doi:10.1002/ijc.11627

    Article  CAS  PubMed  Google Scholar 

  • Cheng YM, Chou CY, Hsu YC, Chen MJ (2012) Influence of HPV16 E6/7 on the expression of FGF2 and FGFR type B in cervical carcinogenesis. Reprod Sci 19:580–586. doi:10.1177/1933719111432874

    Article  PubMed  Google Scholar 

  • Dutt A, Ramos AH, Hammerman PS, Mermel C, Cho J, Sharifnia T, Chande A, Tanaka KE, Stransky N, Greulich H, Gray NS, Meyerson M (2011) Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer. PLoS One 6:e20351. doi:10.1371/journal.pone.0020351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edwards J, Krishna NS, Witton CJ, Bartlett JM (2003) Gene amplifications associated with the development of hormone-resistant prostate cancer. Clin Cancer Res 9:5271–5281

    CAS  PubMed  Google Scholar 

  • Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100:261–269. doi:10.1093/jnci/djn011

    Article  CAS  PubMed  Google Scholar 

  • Freier K, Schwaenen C, Sticht C, Flechtenmacher C, Muhling J, Hofele C, Radlwimmer B, Lichter P, Joos S (2007) Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC). Oral Oncol 43:60–66. doi:10.1016/j.oraloncology.2006.01.005

    Article  CAS  PubMed  Google Scholar 

  • Gillison ML, Lowy DR (2004) A causal role for human papillomavirus in head and neck cancer. Lancet 363:1488–1489. doi:10.1016/S0140-6736(04)16194-1

    Article  CAS  PubMed  Google Scholar 

  • Gorringe KL, Jacobs S, Thompson ER, Sridhar A, Qiu W, Choong DY, Campbell IG (2007) High-resolution single nucleotide polymorphism array analysis of epithelial ovarian cancer reveals numerous microdeletions and amplifications. Clin Cancer Res 13:4731–4739. doi:10.1158/1078-0432.CCR-07-0502

    Article  CAS  PubMed  Google Scholar 

  • Gozgit JM, Wong MJ, Moran L, Wardwell S, Mohemmad QK, Narasimhan NI, Shakespeare WC, Wang F, Clackson T, Rivera VM (2012) Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models. Mol Cancer Ther 11:690–699. doi:10.1158/1535-7163.MCT-11-0450

    Article  CAS  PubMed  Google Scholar 

  • Herrero R, Castellsague X, Pawlita M, Lissowska J, Kee F, Balaram P, Rajkumar T, Sridhar H, Rose B, Pintos J, Fernandez L, Idris A, Sanchez MJ, Nieto A, Talamini R, Tavani A, Bosch FX, Reidel U, Snijders PJ, Meijer CJ, Viscidi R, Munoz N, Franceschi S (2003) Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst 95:1772–1783

    Article  PubMed  Google Scholar 

  • Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ (2008) BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res 68:4774–4782. doi:10.1158/0008-5472.CAN-07-6307

    Article  CAS  PubMed  Google Scholar 

  • Ishizuka T, Tanabe C, Sakamoto H, Aoyagi K, Maekawa M, Matsukura N, Tokunaga A, Tajiri T, Yoshida T, Terada M, Sasaki H (2002) Gene amplification profiling of esophageal squamous cell carcinomas by DNA array CGH. Biochem Biophys Res Commun 296:152–155

    Article  CAS  PubMed  Google Scholar 

  • Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics. CA Cancer J Clin 59:225–249. doi:10.3322/caac.20006

    Article  PubMed  Google Scholar 

  • Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24:2137–2150. doi:10.1200/JCO.2005.05.2308

    Article  PubMed  Google Scholar 

  • Klaes R, Friedrich T, Spitkovsky D, Ridder R, Rudy W, Petry U, Dallenbach-Hellweg G, Schmidt D, von Knebel Doeberitz M (2001) Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer 92:276–284

    Article  CAS  PubMed  Google Scholar 

  • Kohler LH, Mireskandari M, Knosel T, Altendorf-Hofmann A, Kunze A, Schmidt A, Presselt N, Chen Y, Petersen I (2012) FGFR1 expression and gene copy numbers in human lung cancer. Virchows Arch 461:49–57. doi:10.1007/s00428-012-1250-y

    Article  CAS  PubMed  Google Scholar 

  • Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847

    Article  CAS  PubMed  Google Scholar 

  • Ledermann JA, Hackshaw A, Kaye S, Jayson G, Gabra H, McNeish I, Earl H, Perren T, Gore M, Persic M, Adams M, James L, Temple G, Merger M, Rustin G (2011) Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer. J Clin Oncol 29:3798–3804. doi:10.1200/JCO.2010.33.5208

    Article  CAS  PubMed  Google Scholar 

  • Lim SH, Sun JM, Choi YL, Kim HR, Ahn S, Lee JY, Lee SH, Ahn JS, Park K, Kim JH, Cho BC, Ahn MJ (2016) Efficacy and safety of dovitinib in pretreated patients with advanced squamous non-small cell lung cancer with FGFR1 amplification: a single-arm, phase 2 study. Cancer 122:3024–3031. doi:10.1002/cncr.30135

    Article  CAS  PubMed  Google Scholar 

  • Macfarlane TV, Macfarlane GJ, Oliver RJ, Benhamou S, Bouchardy C, Ahrens W, Pohlabeln H, Lagiou P, Lagiou A, Castellsague X, Agudo A, Merletti F, Richiardi L, Kjaerheim K, Slamova A, Schejbalova M, Canova C, Simonato L, Talamini R, Barzan L, Conway DI, McKinney PA, Znaor A, Lowry RJ, Thomson P, Healy CM, McCartan BE, Marron M, Hashibe M, Brennan P (2010) The aetiology of upper aerodigestive tract cancers among young adults in Europe: the ARCAGE study. Cancer Causes Control 21:2213–2221. doi:10.1007/s10552-010-9641-3

    Article  PubMed  Google Scholar 

  • Markovic A, Chung CH (2012) Current role of EGF receptor monoclonal antibodies and tyrosine kinase inhibitors in the management of head and neck squamous cell carcinoma. Expert Rev Anticancer Ther 12:1149–1159. doi:10.1586/era.12.91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marshall ME, Hinz TK, Kono SA, Singleton KR, Bichon B, Ware KE, Marek L, Frederick BA, Raben D, Heasley LE (2011) Fibroblast growth factor receptors are components of autocrine signaling networks in head and neck squamous cell carcinoma cells. Clin Cancer Res 17:5016–5025. doi:10.1158/1078-0432.CCR-11-0050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reis-Filho JS, Simpson PT, Turner NC, Lambros MB, Jones C, Mackay A, Grigoriadis A, Sarrio D, Savage K, Dexter T, Iravani M, Fenwick K, Weber B, Hardisson D, Schmitt FC, Palacios J, Lakhani SR, Ashworth A (2006) FGFR1 emerges as a potential therapeutic target for lobular breast carcinomas. Clin Cancer Res 12:6652–6662. doi:10.1158/1078-0432.CCR-06-1164

    Article  CAS  PubMed  Google Scholar 

  • Schrock A, Goke F, Wagner P, Bode M, Franzen A, Huss S, Agaimy A, Ihrler S, Kirsten R, Kristiansen G, Bootz F, Lengerke C, Perner S (2013) Fibroblast-growth-factor-receptor-1 as a potential therapeutic target in sinonasal cancer? Head Neck. doi:10.1002/hed.23443

    Google Scholar 

  • Simon R, Richter J, Wagner U, Fijan A, Bruderer J, Schmid U, Ackermann D, Maurer R, Alund G, Knonagel H, Rist M, Wilber K, Anabitarte M, Hering F, Hardmeier T, Schonenberger A, Flury R, Jager P, Fehr JL, Schraml P, Moch H, Mihatsch MJ, Gasser T, Sauter G (2001) High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer. Cancer Res 61:4514–4519

    CAS  PubMed  Google Scholar 

  • Sobin LH, Gospodarowicz MK, Wittekind C (2009) TNM classification of malignant tumors. Wiley-Blackwell, New York

    Google Scholar 

  • Sweeny L, Zimmermann TM, Liu Z, Rosenthal EL (2012) Evaluation of tyrosine receptor kinases in the interactions of head and neck squamous cell carcinoma cells and fibroblasts. Oral Oncol. doi:10.1016/j.oraloncology.2012.06.011

    PubMed  PubMed Central  Google Scholar 

  • Turner N, Grose R (2010) Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer 10:116–129. doi:10.1038/nrc2780

    Article  CAS  PubMed  Google Scholar 

  • Weiss J, Sos ML, Seidel D, Peifer M, Zander T, Heuckmann JM, Ullrich RT, Menon R, Maier S, Soltermann A, Moch H, Wagener P, Fischer F, Heynck S, Koker M, Schottle J, Leenders F, Gabler F, Dabow I, Querings S, Heukamp LC, Balke-Want H, Ansen S, Rauh D, Baessmann I, Altmuller J, Wainer Z, Conron M, Wright G, Russell P, Solomon B, Brambilla E, Brambilla C, Lorimier P, Sollberg S, Brustugun OT, Engel-Riedel W, Ludwig C, Petersen I, Sanger J, Clement J, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman D, Cappuzzo F, Ligorio C, Damiani S, Hallek M, Beroukhim R, Pao W, Klebl B, Baumann M, Buettner R, Ernestus K, Stoelben E, Wolf J, Nurnberg P, Perner S, Thomas RK (2010) Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2:62ra93. doi:10.1126/scitranslmed.3001451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young RJ, Lim AM, Angel C, Collins M, Deb S, Corry J, Wiesenfeld D, Kleid S, Sigston E, Lyons B, Russell PA, Wright G, McArthur GA, Fox SB, Rischin D, Solomon B (2013) Frequency of Fibroblast Growth Factor Receptor 1 gene amplification in oral tongue squamous cell carcinomas and associations with clinical features and patient outcome. Oral Oncol. doi:10.1016/j.oraloncology.2013.01.006

    Google Scholar 

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Authors and Affiliations

  1. Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Till Sebastian Clauditz, Guido Sauter & Waldemar Wilczak

  2. Department of Oto-, Rhino, Laryngology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Arne Böttcher & Adrian Münscher

  3. Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Henning Hanken

  4. Department of Radiation-Oncology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Kerstin Borgmann

  5. Institute of Pathology, University Bern, Hochschulstrasse 6, 3012, Bern, Switzerland

    Tobias Grob

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  1. Till Sebastian Clauditz
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Correspondence to Till Sebastian Clauditz.

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Human and animal rights statement

The usage of archived diagnostic left-over tissues for manufacturing of tissue microarrays and their analysis for research purposes as well as patient data analysis has been approved by local laws (HmbKHG, §12,1) and by the local ethics committee (Ethics commission Hamburg, WF-049/09 and PV3652). All works have been carried out in compliance with the Helsinki Declaration. This article does not contain any studies with animals performed by any of the authors.

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Clauditz, T.S., Böttcher, A., Hanken, H. et al. Prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell carcinomas of the head and neck. J Cancer Res Clin Oncol 144, 53–61 (2018). https://doi.org/10.1007/s00432-017-2528-x

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  • DOI: https://doi.org/10.1007/s00432-017-2528-x

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