Abstract
BackgroundThe 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.MethodsFluorescence in situ hybridization and immunohistochemistry were performed to determine FGFR1 gene amplification and protein overexpression in 209 surgically resected cases.ResultsFGFR1 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.ConclusionsFGFR1 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.
Highlights
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)
Most of the studies have been conducted on the whole Head and neck squamous cell carcinoma (HNSCC) showing biological heterogeneity, and site-specific studies have been rarely performed on SCC, especially in SCCs of hypopharynx and larynx, which represent the prevalent subsites of human papilloma virus (HPV)-negative SCC [13,14,15,16,17,18,19]
Regarding the biologic implications of FGFR1 gene amplification or protein overexpression in hypopharyngeal and laryngeal SCC, we investigated a correlation of FGFR1 alteration with twist and snail, the well-known epithelial mesenchymal transition (EMT) markers, on the basis of previous studies showing that EMT is induced in tumors by abnormal activation of the FGFR signaling pathway in several types of cancers including HNSCC [38,39,40,41]
Summary
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). Head and neck squamous cell carcinoma (HNSCC) arises from the squamous mucosa of the upper aerodigestive tract, which comprises the nasal cavity, paranasal sinus, oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx. These distinct anatomic subsites contribute to the morphological, biological, and etiological heterogeneities of HNSCC. The gene encoding FGFR1 is located on chromosome 8p11.23 and encodes tyrosine kinase family, which plays crucial roles in cancer development. This gene is dysregulated by amplification, point mutation, translocation, and overexpression in various cancers [10]. More evidence is needed for the prognostic or predictive role of FGFR1 in HNSCC of hypopharynx and larynx
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