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Published in: Journal of Cancer Research and Clinical Oncology 1/2018

01-01-2018 | Original Article – Cancer Research

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

Authors: Till Sebastian Clauditz, Arne Böttcher, Henning Hanken, Kerstin Borgmann, Guido Sauter, Waldemar Wilczak, Tobias Grob, Adrian Münscher

Published in: Journal of Cancer Research and Clinical Oncology | Issue 1/2018

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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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Literature
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 CrossRefPubMedPubMedCentral 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 CrossRefPubMedPubMedCentral
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference Edwards J, Krishna NS, Witton CJ, Bartlett JM (2003) Gene amplifications associated with the development of hormone-resistant prostate cancer. Clin Cancer Res 9:5271–5281PubMed Edwards J, Krishna NS, Witton CJ, Bartlett JM (2003) Gene amplifications associated with the development of hormone-resistant prostate cancer. Clin Cancer Res 9:5271–5281PubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 95:1772–1783CrossRefPubMed 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 95:1772–1783CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 296:152–155CrossRefPubMed 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 296:152–155CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 92:276–284CrossRefPubMed 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 92:276–284CrossRefPubMed
go back to reference 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 4:844–847CrossRefPubMed 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 4:844–847CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
go back to reference 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 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
go back to reference 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 61:4514–4519PubMed 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 61:4514–4519PubMed
go back to reference Sobin LH, Gospodarowicz MK, Wittekind C (2009) TNM classification of malignant tumors. Wiley-Blackwell, New York Sobin LH, Gospodarowicz MK, Wittekind C (2009) TNM classification of malignant tumors. Wiley-Blackwell, New York
go back to reference 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 CrossRefPubMedPubMedCentral 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 CrossRefPubMedPubMedCentral
go back to reference 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 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
Metadata
Title
Prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell carcinomas of the head and neck
Authors
Till Sebastian Clauditz
Arne Böttcher
Henning Hanken
Kerstin Borgmann
Guido Sauter
Waldemar Wilczak
Tobias Grob
Adrian Münscher
Publication date
01-01-2018
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 1/2018
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-017-2528-x

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