Abstract
Fibroblast growth factor receptor 3 (FGFR3) is expressed in squamous cell carcinoma of the head and neck (SCCHN) including oropharyngeal squamous cell carcinoma (OPSCC) and is a potential therapeutic target. However, information on its correlation with other relevant cancer related proteins stratified by p16 status and its prognostic significance in OPSCC is limited. We examined FGFR3 expression and its correlation with clinical characteristics, p16 status, and mutant p53 (mp53) among 220 retrospectively collected OPSCC cases and 40 prospectively collected SCCHN cases, including a majority of OPSCC. Correlations of FGFR3 Weighted Index (WI) with p16 status and mp53 WI as well as its association with disease-free survival (DFS) and overall survival (OS) were evaluated. FGFR3 expression was detected in 61% and 70% of cases in cohorts 1 and 2, respectively. FGFR3 level was significantly higher in p16-negative tumors in both cohorts (p<0.001 and 0.006). FGFR3 expression was highly correlated with mp53 expression in both p16 + and p16– OPSCC (p<0.0001 and p = 0.0006, respectively). In cohort 1, univariate analysis showed that FGFR3 was associated with DFS but not OS. Kaplan-Meier analysis showed that higher FGFR3 and mp53 level correlated with worse DFS (p = 0.025) and OS (p = 0.009). As expected, p16 positive status was associated with improved OS and DFS (p<0.001 for both). Our results suggest that high FGFR3 expression is associated with p16 negative status and mp53 expression in OPSCC and correlates with a worse clinical outcome. The biological relationship between FGFR3 and mp53 in OPSCC deserves further investigation.
Highlights
According to the American Cancer Society, the mortality rate for squamous cell carcinoma of the head and neck (SCCHN) is decreasing, there has been a rise in oropharyngeal squamous cell carcinoma (OPSCC) due to human papilloma virus (HPV) infection [1, 2]
Fibroblast growth factor receptor 3 (FGFR3) has been studied in SCCHN [10, 22, 23], its expression level has not been carefully
Our findings are the first to confirm a strong correlation between FGFR3 and p16 negative status in SCCHN, as well as an inverse correlation between both mp53 and FGFR3 with p16 status
Summary
According to the American Cancer Society, the mortality rate for squamous cell carcinoma of the head and neck (SCCHN) is decreasing, there has been a rise in oropharyngeal squamous cell carcinoma (OPSCC) due to human papilloma virus (HPV) infection [1, 2]. 65,410 people were estimated to be diagnosed with SCCHN and 14,620 to die of this disease in 2019 [3] HPV-positive SCCHN occurs most frequently in the oropharynx (tonsil and base of tongue), whereas HPV-negative SCCHN occurs in all head and neck sites. It is notable that mutations in one of the most common tumor suppressor proteins, p53, contribute to the development of SCCHN, and wild type p53 has a low expression in HPV-positive tumors [6]. FGFR3 downstream signaling pathways include PI3K/AKT and RAS-MEK-ERK, which are common signaling axes that support cancer cell progression [9]. Increased expression of FGFR3 has been observed in various cancer types including sarcoma, multiple myeloma, breast, prostate, lung, brain, and head and neck cancers [7, 10,11,12,13]. There is no clear evidence that this expression implicates FGFR3 as a possible underlying molecular driver of these cancers
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