The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma

Abstract Background TP53 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 cel...

Full description

Bibliographic Details
Main Authors: Go Omura, Mizuo Ando, Yasuhiro Ebihara, Yuki Saito, Kenya Kobayashi, Osamu Fukuoka, Ken Akashi, Masafumi Yoshida, Takahiro Asakage, Tatsuya Yamasoba
Format: Article
Language:English
Published: BMC 2017-12-01
Series:BMC Cancer
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12885-017-3913-1
_version_ 1811259141945032704
author Go Omura
Mizuo Ando
Yasuhiro Ebihara
Yuki Saito
Kenya Kobayashi
Osamu Fukuoka
Ken Akashi
Masafumi Yoshida
Takahiro Asakage
Tatsuya Yamasoba
author_facet Go Omura
Mizuo Ando
Yasuhiro Ebihara
Yuki Saito
Kenya Kobayashi
Osamu Fukuoka
Ken Akashi
Masafumi Yoshida
Takahiro Asakage
Tatsuya Yamasoba
author_sort Go Omura
collection DOAJ
description Abstract Background TP53 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. Methods We 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. Results TP53 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). Conclusion The 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.
first_indexed 2024-04-12T18:27:00Z
format Article
id doaj.art-1238d96f671a4ffcb48997820f085a0d
institution Directory Open Access Journal
issn 1471-2407
language English
last_indexed 2024-04-12T18:27:00Z
publishDate 2017-12-01
publisher BMC
record_format Article
series BMC Cancer
spelling doaj.art-1238d96f671a4ffcb48997820f085a0d2022-12-22T03:21:13ZengBMCBMC Cancer1471-24072017-12-0117111010.1186/s12885-017-3913-1The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinomaGo Omura0Mizuo Ando1Yasuhiro Ebihara2Yuki Saito3Kenya Kobayashi4Osamu Fukuoka5Ken Akashi6Masafumi Yoshida7Takahiro Asakage8Tatsuya Yamasoba9Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of TokyoDepartment of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of TokyoDepartment of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of TokyoDepartment of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of TokyoDepartment of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of TokyoDepartment of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of TokyoDepartment of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of TokyoDepartment of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of TokyoDepartment of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of TokyoDepartment of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of TokyoAbstract Background TP53 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. Methods We 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. Results TP53 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). Conclusion The 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.http://link.springer.com/article/10.1186/s12885-017-3913-1TP53 mutationHypopharyngeal squamous cell carcinomaTruncating mutationPrognosisPharyngectomy
spellingShingle Go Omura
Mizuo Ando
Yasuhiro Ebihara
Yuki Saito
Kenya Kobayashi
Osamu Fukuoka
Ken Akashi
Masafumi Yoshida
Takahiro Asakage
Tatsuya Yamasoba
The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma
BMC Cancer
TP53 mutation
Hypopharyngeal squamous cell carcinoma
Truncating mutation
Prognosis
Pharyngectomy
title The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma
title_full The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma
title_fullStr The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma
title_full_unstemmed The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma
title_short The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma
title_sort prognostic value of tp53 mutations in hypopharyngeal squamous cell carcinoma
topic TP53 mutation
Hypopharyngeal squamous cell carcinoma
Truncating mutation
Prognosis
Pharyngectomy
url http://link.springer.com/article/10.1186/s12885-017-3913-1
work_keys_str_mv AT goomura theprognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT mizuoando theprognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT yasuhiroebihara theprognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT yukisaito theprognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT kenyakobayashi theprognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT osamufukuoka theprognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT kenakashi theprognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT masafumiyoshida theprognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT takahiroasakage theprognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT tatsuyayamasoba theprognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT goomura prognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT mizuoando prognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT yasuhiroebihara prognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT yukisaito prognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT kenyakobayashi prognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT osamufukuoka prognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT kenakashi prognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT masafumiyoshida prognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT takahiroasakage prognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma
AT tatsuyayamasoba prognosticvalueoftp53mutationsinhypopharyngealsquamouscellcarcinoma