Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr 18;20(1):348.
doi: 10.1186/s12885-020-06792-7.

Prognostic implications of Fibroblast growth factor receptor 1 (FGFR1) gene amplification and protein overexpression in hypopharyngeal and laryngeal squamous cell carcinoma

Eun Kyung Kim  1 , Yoon Ah Cho  2   3 , Yoon Woo Koh  4 , Hyang Ae Shin  5 , Byoung Chul Cho  6 , Sun Och Yoon  7
Affiliations

Prognostic implications of Fibroblast growth factor receptor 1 (FGFR1) gene amplification and protein overexpression in hypopharyngeal and laryngeal squamous cell carcinoma

Eun Kyung Kim et al. BMC Cancer. .

Abstract

Background: The gene encoding fibroblast growth factor receptor 1 (FGFR1) is emerging as a therapeutic and prognostic biomarker in various cancer types, including head and neck squamous cell carcinoma (SCC). Here, we investigated the clinicopathologic implication of FGFR1 gene amplification and protein overexpression in hypopharyngeal and laryngeal SCC.

Methods: Fluorescence in situ hybridization and immunohistochemistry were performed to determine FGFR1 gene amplification and protein overexpression in 209 surgically resected cases.

Results: FGFR1 amplification observed in 8 (8/66, 12.1%; 6 hypopharynx and 2 larynx) patients and high FGFR1 expression in 21 (21/199, 10.6%) patients significantly correlated with lymph node metastasis and advanced pathological stages. FGFR1 amplification was also associated with worse disease-free survival in multivariate analysis (hazard ratio = 4.527, P = 0.032). High FGFR1 expression was more frequently observed, consistent with the worsening of the degree of histologic differentiation.

Conclusions: FGFR1 amplification may serve as an independent prognostic factor for disease-free survival in hypopharyngeal and laryngeal SCC. Aberrant FGFR signaling caused by FGFR1 gene amplification or protein overexpression may play a crucial role in the malignant evolution and progression of hypopharyngeal and laryngeal SCC, and offer novel therapeutic opportunities in patients with hypopharyngeal and laryngeal SCC that usually lack specific therapeutic targets.

Keywords: Amplification; Fibroblast growth factor receptor 1 (FGFR1); Fluorescence in situ hybridization; Hypopharynx; Immunohistochemistry; Larynx; Squamous cell carcinoma.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
FGFR1 FISH analysis and FGFR1 protein expression in hypopharyngeal and laryngeal squamous cell carcinoma (SCC). (a) Amplified FGFR1 expression is shown as red signals (yellow arrows) and CEP8 signal (white arrows) is shown as green in nuclei. Increased red signals (in number 3~6) compared to green signal (in number 1~2) could define amplification of FGFR1 gene. Scale bar represents 10 μm. (original magnification, 1000×). Representative FGFR1 immunohistochemical staining (original magnification, 200×) showing negative (b), low expression (c), and high expression (d), and the corresponding hematoxylin and eosin-stained cases (inset; original magnification 400×) showing well differentiated SCC (b), moderately differentiated SCC (c), and poorly differentiated SCC (d)
Fig. 2
Fig. 2
FGFR1 immunohistochemistry in hypopharyngeal and laryngeal squamous cell carcinoma. (a) FGFR1-positive tumor cells with strong intensity were observed in more than 80% tumor area. (b) High FGFR1 expression was more frequently found in poorly differentiated histology. (c) High FGFR1 protein expression showed a marginal tendency to be related to gene amplification
Fig. 3
Fig. 3
Kaplan-Meier survival curves for FGFR1 gene amplification (a and b) and protein overexpression (c and d) in hypopharyngeal and laryngeal squamous cell carcinoma. FGFR1 amplification was significantly associated with disease-free survival (a) but not overall survival (b). FGFR1 protein overexpression was not related to disease-free survival (c) or overall survival (d)
See this image and copyright information in PMC

References

    1. Hashibe M, Brennan P, Benhamou S, Castellsague X, Chen C, Curado MP, Dal Maso L, Daudt AW, Fabianova E, Fernandez L, et al. Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the international head and neck Cancer epidemiology consortium. J Natl Cancer Inst. 2007;99(10):777–789. doi: 10.1093/jnci/djk179. - DOI - PubMed
    1. El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. WHO classification of head and neck Tumours. 4. Lyon: International Agency for Research on Cancer; 2017.
    1. Gillison ML, D'Souza G, Westra W, Sugar E, Xiao W, Begum S, Viscidi R. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. 2008;100(6):407–420. doi: 10.1093/jnci/djn025. - DOI - PubMed
    1. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35. doi: 10.1056/NEJMoa0912217. - DOI - PMC - PubMed
    1. Posner MR, Lorch JH, Goloubeva O, Tan M, Schumaker LM, Sarlis NJ, Haddad RI, Cullen KJ. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. Ann Oncol. 2011;22(5):1071–1077. doi: 10.1093/annonc/mdr006. - DOI - PMC - PubMed

MeSH terms

Substances