PMID- 32275333
OWN - NLM
STAT- MEDLINE
DCOM- 20201023
LR  - 20201023
IS  - 1531-4995 (Electronic)
IS  - 0023-852X (Print)
IS  - 0023-852X (Linking)
VI  - 130
IP  - 8
DP  - 2020 Aug
TI  - High pATM is Associated With Poor Local Control in Supraglottic Cancer Treated 
      With Radiotherapy.
PG  - 1954-1960
LID - 10.1002/lary.28641 [doi]
AB  - OBJECTIVES: Most early stage laryngeal squamous cell carcinomas (LSCC) are 
      treated with radiotherapy. Discovery of new biomarkers are needed to improve 
      prediction of outcome after radiotherapy and to identify potential targets for 
      systemic targeted therapy. The ataxia telangiectasia mutated (ATM) gene plays a 
      critical role in DNA damage response induced by ionizing radiation. METHODS: The 
      prognostic value of immunohistochemical expression of pATM, pChk2, and p53 were 
      investigated in 141 patients with T1-T2 LSCC curatively treated with external 
      beam radiotherapy. Uni- and multivariable Cox regression analyses were performed 
      to examine the relation between expression levels of markers and local control. 
      RESULTS: Local control was significantly worse in cases with high levels of pATM 
      (HR 2.14; 95% CI, 1.08-4.24; P = .03). No significant associations with local 
      control were found for pChk2 and p53 expression. The association of high pATM 
      expression with poor local control was only found for supraglottic LSCC (HR 10.9; 
      95% CI, 1.40-84.4; P = .02). CONCLUSION: Our findings suggest a potential role 
      for ATM in response to radiotherapy in early stage supraglottic LSCC and imply 
      ATM inhibition as a possibility to improve response to radiotherapy. LEVEL OF 
      EVIDENCE: NA Laryngoscope, 130: 1954-1960, 2020.
CI  - (c) 2020 The Authors. The Laryngoscope published by Wiley Periodicals, Inc. on 
      behalf of The American Laryngological, Rhinological and Otological Society, Inc.
FAU - Bruine de Bruin, Leonie
AU  - Bruine de Bruin L
AUID- ORCID: 0000-0003-1240-9236
AD  - Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, 
      University Medical Center Groningen, Groningen, The Netherlands.
FAU - Schuuring, Ed
AU  - Schuuring E
AD  - Department of Pathology and Medical Biology, University of Groningen, University 
      Medical Center Groningen, Groningen, The Netherlands.
FAU - de Bock, Geertruida H
AU  - de Bock GH
AD  - Department of Epidemiology and Statistics, University of Groningen, University 
      Medical Center Groningen, Groningen, The Netherlands.
FAU - Slagter-Menkema, Lorian
AU  - Slagter-Menkema L
AD  - Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, 
      University Medical Center Groningen, Groningen, The Netherlands.
AD  - Department of Pathology and Medical Biology, University of Groningen, University 
      Medical Center Groningen, Groningen, The Netherlands.
FAU - Mastik, Mirjam F
AU  - Mastik MF
AD  - Department of Pathology and Medical Biology, University of Groningen, University 
      Medical Center Groningen, Groningen, The Netherlands.
FAU - Noordhuis, Maartje G
AU  - Noordhuis MG
AD  - Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, 
      University Medical Center Groningen, Groningen, The Netherlands.
FAU - Langendijk, Johannes A
AU  - Langendijk JA
AD  - Department of Radiation Oncology, University of Groningen, University Medical 
      Center Groningen, Groningen, The Netherlands.
FAU - Kluin, Philip M
AU  - Kluin PM
AD  - Department of Pathology and Medical Biology, University of Groningen, University 
      Medical Center Groningen, Groningen, The Netherlands.
FAU - van der Laan, Bernard F A M
AU  - van der Laan BFAM
AUID- ORCID: 0000-0002-5016-2871
AD  - Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, 
      University Medical Center Groningen, Groningen, The Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20200410
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.1.11 (Checkpoint Kinase 2)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Ataxia Telangiectasia Mutated Proteins/*genetics
MH  - Biomarkers, Tumor/*genetics
MH  - Carcinoma, Squamous Cell/*genetics/*pathology/*radiotherapy
MH  - Checkpoint Kinase 2/genetics
MH  - Female
MH  - Humans
MH  - Laryngeal Neoplasms/*pathology/*radiotherapy
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Tumor Suppressor Protein p53/genetics
PMC - PMC7384019
OTO - NOTNLM
OT  - Laryngeal squamous cell carcinoma
OT  - ataxia telangiectasia mutated (ATM)
OT  - local control
OT  - radiotherapy
EDAT- 2020/04/11 06:00
MHDA- 2020/10/24 06:00
PMCR- 2020/07/27
CRDT- 2020/04/11 06:00
PHST- 2019/11/17 00:00 [received]
PHST- 2020/02/09 00:00 [revised]
PHST- 2020/03/02 00:00 [accepted]
PHST- 2020/04/11 06:00 [pubmed]
PHST- 2020/10/24 06:00 [medline]
PHST- 2020/04/11 06:00 [entrez]
PHST- 2020/07/27 00:00 [pmc-release]
AID - LARY28641 [pii]
AID - 10.1002/lary.28641 [doi]
PST - ppublish
SO  - Laryngoscope. 2020 Aug;130(8):1954-1960. doi: 10.1002/lary.28641. Epub 2020 Apr 
      10.