Abstract
BackgroundTP53 is the most frequently mutated gene in human cancers. Previous studies reported that TP53 mutations correlated with poor prognoses in patients with head and neck squamous cell carcinoma (HNSCC). However, the relationship between TP53 mutations and hypopharyngeal squamous cell carcinoma (HPSCC) is not known. The current study aimed to evaluate TP53 mutation status as a predictive biomarker in patients with HPSCC.MethodsWe retrospectively reviewed the clinical charts of 57 HPSCC patients treated with initial surgery between 2008 and 2014. TP53 mutation status was determined by Sanger sequencing, and patients were classified into wild-type, missense mutation, and truncating mutation groups. Additionally, p53 expression was determined using immunohistochemistry in surgical specimens.ResultsTP53 mutations were identified in 39 (68%) patients. The 3-year disease-specific survival (DSS) rate of wild-type, missense mutation, and truncating mutation group were 94%, 61%, and 43%, respectively. The TP53 mutation group displayed significantly worse DSS and overall survival rates than the wild-type group (P = 0.01 and P = 0.007, respectively). Multivariate analyses revealed that the presence of TP53 mutations and ≥4 metastatic lymph nodes were independent adverse prognostic factors for HPSCC. p53 immunopositivity was detected in 22 patients, including 5 (28%) and 17 (71%) patients in the wild-type and missense mutation groups, whereas none of the patients with truncating mutation exhibited p53 immunopositivity (P = 0.0001).ConclusionThe TP53 mutation status correlated with poor prognosis in surgically treated HPSCC patients. Specifically, truncating mutations which were not detected by p53 immunohistochemistry were predictive of worst survival.
Highlights
TP53 is the most frequently mutated gene in human cancers
Human papillomavirus status of patients with hypopharyngeal squamous cell carcinoma In this cohort of 57 HPSCC patients, 3 (5%) patients were immunopositive for p16; none of these three patients had detectable human papillomavirus (HPV) DNA by HPV-in situ hybridization (ISH)
All of stage I/II patients (5 patients) had wild-type TP53, and patients with a past history of head and neck squamous cell carcinoma (HNSCC) or esophageal squamous cell carcinomas (SCC) (ESCC) were significantly greater in the TP53 mutation groups than in the wild-type groups (P = 0.02)
Summary
Previous studies reported that TP53 mutations correlated with poor prognoses in patients with head and neck squamous cell carcinoma (HNSCC). The relationship between TP53 mutations and hypopharyngeal squamous cell carcinoma (HPSCC) is not known. Glu504Lys (previously described as Glu487Lys), which is prevalent in Mongoloid but not in Caucasoid or Negroid populations [2] This different genetic background is considered as a major reason of high HPSCC and ESCC incidence rates in East Asia [3, 4]. Tumor suppressor p53, encoded by the TP53 gene, is a key protein involved in many cellular anticarcinogenic processes such as apoptosis and cell-cycle control [7]; p53 is widely known as the guardian of the genome [8]. Molecular alterations in carcinogenesis of HNSCC include loss of p53 function, which is mediated by genetic mechanisms such as TP53 mutations [9] and loss
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