PMID- 34427325
OWN - NLM
STAT- MEDLINE
DCOM- 20220418
LR  - 20220731
IS  - 1531-4995 (Electronic)
IS  - 0023-852X (Print)
IS  - 0023-852X (Linking)
VI  - 132
IP  - 4
DP  - 2022 Apr
TI  - High DNMT1 Is Associated With Worse Local Control in Early-Stage Laryngeal 
      Squamous Cell Carcinoma.
PG  - 801-805
LID - 10.1002/lary.29833 [doi]
AB  - OBJECTIVES/HYPOTHESIS: Early-stage laryngeal squamous cell carcinoma (LSCC) has 
      yielded local control rates of 75% after radiotherapy. DNA methylation, in which 
      DNA methyltransferases play an important role, has influence on tumorigenesis. In 
      this study, we investigated the association between the expression of DNA 
      methyltransferase 1 (DNMT1) and local control in early-stage LSCC treated with 
      radiotherapy. STUDY DESIGN: Retrospective cohort study. METHODS: We analyzed a 
      well-defined homogeneous series of 125 LSCC patients treated with radiotherapy 
      with curative intent. The association of immunohistochemical expression of DNMT1 
      with local control was evaluated using Cox proportional hazard regression models. 
      RESULTS: With a median follow-up of 58 months, 29 local recurrences (23%) were 
      observed. On univariate analysis, worse local control was associated with high 
      DNMT1 expression (hazard ratio [HR] 2.57, 95% confidence interval [CI] 
      1.10-6.01). Also, higher T-stage (HR 2.48, 95% CI 1.06-5.80) and positive 
      N-status (HR 2.62, 95% CI 1.06-6.47) were associated with worse local control. 
      Multivariate Cox regression demonstrated that high DNMT1 (HR 2.81; 95% CI 
      1.20-6.58) was independently associated with worse local control. CONCLUSIONS: We 
      found an association between high DNMT1 expression and worse local control in a 
      homogeneous well-defined cohort of early-stage LSCC patients treated with 
      definitive radiotherapy. The association between DNA methylation status as 
      determined by DNMT1 expression and local control suggests that DNMT1 acts as a 
      potential prognostic tumor marker in treatment decision-making in early-stage 
      laryngeal carcinoma. LEVEL OF EVIDENCE: NA Laryngoscope, 132:801-805, 2022.
CI  - (c) 2021 The Authors. The Laryngoscope published by Wiley Periodicals LLC 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.
AD  - Department of Pathology and Medical Biology, University of Groningen, University 
      Medical Center Groningen, Groningen, The Netherlands.
FAU - Clausen, Martijn J A M
AU  - Clausen MJAM
AD  - Department of Pathology and Medical Biology, University of Groningen, University 
      Medical Center Groningen, Groningen, The Netherlands.
AD  - Department of Epidemiology, 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 - de Bock, Gertruida H
AU  - de Bock GH
AD  - Department of Epidemiology, 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 - van der Vegt, Bert
AU  - van der Vegt B
AUID- ORCID: 0000-0002-2613-1506
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.
FAU - Schuuring, Ed
AU  - Schuuring E
AD  - Department of Pathology and Medical Biology, University of Groningen, University 
      Medical Center Groningen, Groningen, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210824
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - *Carcinoma, Squamous Cell/genetics/metabolism/radiotherapy
MH  - DNA
MH  - *Head and Neck Neoplasms/pathology
MH  - Humans
MH  - *Laryngeal Neoplasms/genetics/metabolism/radiotherapy
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Retrospective Studies
MH  - Squamous Cell Carcinoma of Head and Neck/pathology
PMC - PMC9290472
OTO - NOTNLM
OT  - DNA methylation
OT  - Laryngeal squamous cell carcinoma
OT  - local control
OT  - prognostic marker
OT  - radiotherapy
EDAT- 2021/08/25 06:00
MHDA- 2022/04/19 06:00
PMCR- 2022/07/18
CRDT- 2021/08/24 09:24
PHST- 2021/08/08 00:00 [revised]
PHST- 2021/05/09 00:00 [received]
PHST- 2021/08/10 00:00 [accepted]
PHST- 2021/08/25 06:00 [pubmed]
PHST- 2022/04/19 06:00 [medline]
PHST- 2021/08/24 09:24 [entrez]
PHST- 2022/07/18 00:00 [pmc-release]
AID - LARY29833 [pii]
AID - 10.1002/lary.29833 [doi]
PST - ppublish
SO  - Laryngoscope. 2022 Apr;132(4):801-805. doi: 10.1002/lary.29833. Epub 2021 Aug 24.