Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Targeted Oncology
Published in: Targeted Oncology 1/2016

Open Access 01-02-2016 | Review Article

Fibroblast Growth Factor Receptor Family Members as Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review

Authors: Norbertus A. Ipenburg, Koos Koole, K. Seng Liem, Pauline M. W. van Kempen, Ron Koole, Paul J. van Diest, Robert J. J. van Es, Stefan M. Willems

Published in: Targeted Oncology | Issue 1/2016

Login to get access

Abstract

Background

Since head and neck cancer is characterized by poor survival rates, there is a demand for novel therapeutic targets and prognostic biomarkers. An upcoming therapeutic target is the fibroblast growth factor receptor (FGFR) family. However, their prognostic role in head and neck cancer remains unclear.

Objective

To systematically review current evidence on the prognostic value of FGFR family members in head and neck squamous cell carcinoma (HNSCC).

Methods

A systematic search of PubMed, Embase, and the Cochrane Library was performed for publications up to 14 May 2014. Two reviewers screened all articles and included prognostic studies on the molecular biomarkers FGFR1-5 in any type of HNSCC. Relevant studies were assessed on risk of bias using the Quality in Prognostic Studies (QUIPS) tool. Data on FGFR aberrations and survival outcome were extracted from relevant studies. The prognostic value of FGFR aberrations was compared among studies.

Results

The initial search yielded 1568 publications of which 12 fulfilled the inclusion criteria. Four studies reported FGFR1 gene amplification (9.3–17.4 %) and FGFR1 protein overexpression (11.8 %) in HNSCC. FGFR1 protein expression by cancer-associated fibroblasts correlated with poor survival outcome in one study (p < 0.01). Eight studies reported high rates of FGFR4 Gly388Arg polymorphisms (32.5–54.2 %) and FGFR4 protein overexpression (16–35 %), with varying correlations with survival. So far, no studies assessed the prognostic role of FGFR2, FGFR3, or FGFR5 in HNSCC.

Limitations

Significant risk of bias has been identified among included studies. Therefore, cautious interpretation of the results is recommended.

Conclusion

In conclusion, evidence was found for prognostic value of FGFR1 expression in cancer-associated fibroblasts in HNSCC. Prognostic evidence on the other FGFR family members in HNSCC is limited and conflicting. This emphasizes the need for future well-conducted prognostic studies.
Appendix
Available only for authorised users
Literature
1.
Argiris A, Karamouzis MV, Raben D, Ferris RL (2003) Head and neck cancer. Lancet 71:1695–709
2.
Pulte D, Brenner H (2010) Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist 15:994–1001CrossRefPubMedPubMedCentral
3.
Seiwert TY, Zuo Z, Keck MK et al (2014) Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res 21:632–41
4.
Van Kempen PM, Noorlag R, Braunius WW et al (2014) Differences in methylation profiles between HPV-positive and HPV-negative oropharynx squamous cell carcinoma: a systematic review. Epigenetics 9:194–203CrossRefPubMed
5.
Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11:9–22CrossRefPubMed
6.
Conley BA (2006) Treatment of advanced head and neck cancer: what lessons have we learned? J Clin Oncol 24:1023–5CrossRefPubMed
7.
Noorlag R, van der Groep P, Leusink FK et al (2014) Nodal metastasis and survival in oral cancer: association with protein expression of SLPI, not with LCN2, TACSTD2, or THBS2. Head Neck. doi:10.​1002/​hed.​23716 PubMed
8.
9.
Dienstmann R, Rodon J, Prat A et al (2014) Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors. Ann Oncol 25:552–63CrossRefPubMed
10.
11.
Powers CJ, McLeskey SW, Wellstein A (2000) Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer 7:165–97CrossRefPubMed
12.
Hughes SE (1997) Differential expression of the fibroblast growth factor receptor (FGFR) multigene family in normal human adult tissues. J Histochem Cytochem 45:1005–19CrossRefPubMed
13.
Daniele G, Corral J, Molife LR, de Bono JS (2012) FGF receptor inhibitors: role in cancer therapy. Curr Oncol Rep 14:111–9CrossRefPubMed
14.
15.
Haugsten EM, Wiedlocha A, Olsnes S, Wesche J (2010) Roles of fibroblast growth factor receptors in carcinogenesis. Mol Cancer Res 8:1439–52CrossRefPubMed
16.
Parker BC, Engels M, Annala M, Zhang W (2014) Emergence of FGFR family gene fusions as therapeutic targets in a wide spectrum of solid tumours. J Pathol 232:4–15CrossRefPubMed
17.
Dieci MV, Arnedos M, Andre F, Soria JC (2013) Fibroblast growth factor receptor inhibitors as a cancer treatment: from a biologic rationale to medical perspectives. Cancer Discov 3:264–79CrossRefPubMed
18.
Dutra RL, de Carvalho MB, Dos Santos M et al (2012) FGFR4 profile as a prognostic marker in squamous cell carcinoma of the mouth and oropharynx. PLoS One 7, e50747CrossRefPubMedPubMedCentral
19.
Da Costa Andrade VC, Parise O, Hors CP et al (2007) The fibroblast growth factor receptor 4 (FGFR4) Arg388 allele correlates with survival in head and neck squamous cell carcinoma. Exp Mol Pathol 82:53–7CrossRefPubMed
20.
Hayden JA, Côté P, Bombardier C (2006) Evaluation of the quality of prognosis studies in systematic reviews. Ann Intern Med 144:427–37CrossRefPubMed
21.
Hayden JA, van der Windt DA, Cartwright JL et al (2013) Assessing bias in studies of prognostic factors. Ann Intern Med 158:280–6CrossRefPubMed
22.
Chen GL, Luo LH, Ding J (2006) Expression of basic fibroblast growth factor and its double receptors in laryngeal squamous cell carcinoma and its significance. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 41:301–2PubMed
23.
Choi KY, Rho YS, Kwon KH et al (2013) ECRG1 and FGFR4 single nucleotide polymorphism as predictive factors for nodal metastasis in oral squamous cell carcinoma. Cancer Biomark 12:115–24
24.
Göke F, Bode M, Franzen A et al (2013) Fibroblast growth factor receptor 1 amplification is a common event in squamous cell carcinoma of the head and neck. Mod Pathol 26:1298–306CrossRefPubMed
25.
Young RJ, Lim AM, Angel C et al (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 49:576–81CrossRefPubMed
26.
Freier K, Schwaenen C, Sticht C et al (2007) Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC). Oral Oncol 43:60–6CrossRefPubMed
27.
Hase T, Kawashiri S, Tanaka A et al (2006) Correlation of basic fibroblast growth factor expression with the invasion and the prognosis of oral squamous cell carcinoma. J Oral Pathol Med 35:136–9CrossRefPubMed
28.
Farnebo L, Tiefenböck K, Ansell A et al (2013) Strong expression of survivin is associated with positive response to radiotherapy and improved overall survival in head and neck squamous cell carcinoma patients. Int J Cancer 133:1994–2003CrossRefPubMed
29.
Azad AK, Bairati I, Samson E et al (2012) Validation of genetic sequence variants as prognostic factors in early-stage head and neck squamous cell cancer survival. Clin Cancer Res 18:196–206CrossRefPubMed
30.
Tanuma J, Izumo T, Hirano M et al (2010) FGFR4 polymorphism, TP53 mutation, and their combinations are prognostic factors for oral squamous cell carcinoma. Oncol Rep 23:739–44PubMed
31.
Ansell A, Farnebo L, Grénman R, Roberg K, Thunell LK (2009) Polymorphism of FGFR4 in cancer development and sensitivity to cisplatin and radiation in head and neck cancer. Oral Oncol 45:23–9CrossRefPubMed
32.
Streit S, Bange J, Fichtner A et al (2004) Involvement of the FGFR4 Arg388 allele in head and neck squamous cell carcinoma. Int J Cancer 111:213–7CrossRefPubMed
33.
Motahhary P, Baghaie F, Mamishi S et al (2012) Mutational status of FGFR3 in oral squamous cell carcinoma. J Dent (Tehran) 9:7–13
34.
Zhang Y, Hiraishi Y, Wang H et al (2005) Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas. Int J Cancer 117:166–8CrossRefPubMed
35.
36.
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 48:1242–9CrossRefPubMedPubMedCentral
37.
38.
Wakulich C, Jackson-Boeters L, Daley TD, Wysocki GP (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. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93:573–9CrossRefPubMed
39.
Dellacono FR, Spiro J, Eisma R, Kreutzer D (1997) Expression of basic fibroblast growth factor and its receptors by head and neck squamous carcinoma tumor and vascular endothelial cells. Am J Surg 174:540–4CrossRefPubMed
40.
41.
Craddock KJ, Ludkovski O, Sykes J, Shepherd FA, Tsao M (2013) Prognostic value of fibroblast growth factor receptor 1 gene locus amplification in resected lung squamous cell carcinoma. J Thorac Oncol 8:1371–7CrossRefPubMed
42.
Russell PA, Yu Y, Young RJ et al (2014) Prevalence, morphology, and natural history of FGFR1-amplified lung cancer, including squamous cell carcinoma, detected by FISH and SISH. Mod Pathol. doi:10.​1038/​modpathol.​2014.​71 PubMed
43.
Kim HR, Kim DJ, Kang DR et al (2013) Fibroblast growth factor receptor 1 gene amplification is associated with poor survival and cigarette smoking dosage in patients with resected squamous cell lung cancer. J Clin Oncol 31:731–7CrossRefPubMed
44.
Cihoric N, Savic S, Schneider S et al (2014) Prognostic role of FGFR1 amplification in early-stage non-small cell lung cancer. Br J Cancer 110:2914–22CrossRefPubMedPubMedCentral
45.
46.
Bange J, Prechtl D, Cheburkin Y et al (2002) Cancer progression and tumor cell motility are associated with the FGFR4 Arg 388 allele. Cancer Res 62:840–7PubMed
47.
Thussbas C, Nahrig J, Streit S et al (2006) FGFR4 Arg388 allele is associated with resistance to adjuvant therapy in primary breast cancer. J Clin Oncol 24:3747–55CrossRefPubMed
48.
49.
Spinola M, Leoni VP, Tanuma J et al (2005) FGFR4 Gly388Arg polymorphism and prognosis of breast and colorectal cancer. Oncol Rep 14:415–9PubMed
50.
Liu X, Zhang W, Geng D et al (2014) Clinical significance of fibroblast growth factor receptor-3 mutations in bladder cancer: a systematic review and meta-analysis. Genet Mol Res 13:1109–20CrossRefPubMed
51.
Hammerman PS, Hayes DN, Grandis JR (2015) Therapeutic insights from genomic studies of head and neck squamous cell carcinomas. Cancer Discov 5:239–44CrossRefPubMedPubMedCentral
52.
André F, Bachelot T, Campone M et al (2013) Targeting FGFR with dovitinib (TKI258): preclinical and clinical data in breast cancer. Clin Cancer Res 19:3693–702CrossRefPubMed
53.
The Cancer Genome Atlas Network (2015) Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517:576–82CrossRefPubMedCentral
54.
Uzawa K, Ishigami T, Fushimi K et al (2011) Targeting fibroblast growth factor receptor 3 enhances radiosensitivity in human squamous cancer cells. Oncogene 30:4447–52CrossRefPubMed
55.
Roidl A, Berger H, Kumar S et al (2009) Resistance to chemotherapy is associated with fibroblast growth factor receptor 4 up-regulation. Clin Cancer Res 15:2058–66CrossRefPubMed
56.
Turkington RC, Longley DB, Allen WL et al (2014) Fibroblast growth factor receptor 4 (FGFR4): a targetable regulator of drug resistance in colorectal cancer. Cell Death Dis 5, e1046CrossRefPubMedPubMedCentral
Metadata
Title
Fibroblast Growth Factor Receptor Family Members as Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review
Authors
Norbertus A. Ipenburg
Koos Koole
K. Seng Liem
Pauline M. W. van Kempen
Ron Koole
Paul J. van Diest
Robert J. J. van Es
Stefan M. Willems
Publication date
01-02-2016
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 1/2016
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-015-0374-9

Other articles of this Issue 1/2016

Targeted Oncology 1/2016 Go to the issue

Original Research

Secondary Metastases Resection After Bevacizumab Plus Irinotecan-Based Chemotherapy in First-Line Therapy of Metastatic Colorectal Cancer in a Real-Life Setting: Results of the ETNA Cohort

Original Research

Vemurafenib pharmacokinetics and its correlation with efficacy and safety in outpatients with advanced BRAF-mutated melanoma

Letter to the Editor

Comment on: “Regorafenib: Start Low and Go Slow”

Letter to the Editor

Author’s Reply to Christelle de la Fouchardière: “Regorafenib: Start Low and Go Slow”

Adis Drug Evaluation

Panobinostat: A Review in Relapsed or Refractory Multiple Myeloma

Adis Drug Evaluation

Lenvatinib: A Review in Refractory Thyroid Cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits