Association Between Fibroblast Growth Factor Receptor 1 Gene Amplification and Human Papillomavirus Prevalence in Tonsillar Squamous Cell Carcinoma With Clinicopathologic Analysis

Abstract

Amplification of fibroblast growth factor receptor 1 ( FGFR1) has been reported in many squamous cell carcinomas, and human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma has been characterized as a distinct subset with favorable prognosis. Here, we investigated the FGFR1 amplification and HPV status in tonsillar squamous cell carcinoma (TSCC) and analyzed the clinical characteristics. HPV in situ hybridization (HPV ISH) and FGFR1 fluorescence in situ hybridization (FISH) were performed using tissue microarray from 89 cases of TSCC. Fourteen of 89 (15.7%) TSCC cases had FGFR1 amplification, and HPV was detected in 59 of 89 (66.3%) cases. FGFR1 amplification status was not associated with HPV positivity ( p=0.765). Outcomes were not significantly different between FGFR1 amplified and non-amplified patients. Although FGFR1 amplified patients ( n=4) in the HPV ISH-negative group ( n=30) had a tendency for poorer overall survival, no statistical significance was identified ( p=0.150, log-rank). FGFR1 protein overexpression showed better disease-free survival ( p=0.031, log-rank) in HPV-negative TSCC. This study suggests FGFR1 amplification may be important in the pathogenesis of TSCC regardless of HPV status.

Keywords: fibroblast growth factor receptor 1; fluorescence in situ hybridization; human papillomavirus; squamous cell carcinoma; tonsil.

Figure 1.

Study cohort flow diagram.

Figure 2.

Representative images of FGFR1 expression from negative (score 0, A), weakly positive (score 1, B), and intermediately positive (score 2, C) to strongly positive (score 3, D) are shown by immunohistochemistry. Scale bar represents 50 µm. Abbreviation: FGFR1, fibroblast growth factor receptor 1.

Figure 3.

FGFR1 gene copy number assessment by FISH. (A) The cells show FGFR1 gene amplification. (B) The cells show normal disomic signals. Scale bar represents 10 µm. Abbreviations: FGFR1, fibroblast growth factor receptor 1; FISH, fluorescence in situ hybridization.

Figure 4.

OS and DFS for FGFR1 gene amplification determined by FISH. (A, B) FGFR1 amplification is not associated with prognosis. (C, D) When restricting analysis to the HPV-negative group only (n=30), there is still no association with OS (C) or DFS (D). (E, F) When restricting the analysis to smokers (n=53), there is no association with OS (E) or DFS (F). Abbreviations: OS, overall survival; DFS, disease-free survival; FGFR1, fibroblast growth factor receptor 1; FISH, fluorescence in situ hybridization; HPV, human papillomavirus.

Figure 5.

Survival analysis for FGFR1 protein expression in patients with HPV in situ hybridization negativity. FGFR1 is a poor prognostic factor for recurrence (p=0.031, log-rank, B), while no prognostic significance is observed in overall survival (p=0.076, log-rank, A). Abbreviations: FGFR1, fibroblast growth factor receptor 1; HPV, human papillomavirus.