High DNMT1 Is Associated With Worse Local Control in Early-Stage Laryngeal Squamous Cell Carcinoma.

Autor: Bruine de Bruin L; Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Clausen MJAM; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Slagter-Menkema L; Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., de Bock GH; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Langendijk JA; Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., van der Vegt B; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., van der Laan BFAM; Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Schuuring E; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: The Laryngoscope [Laryngoscope] 2022 Apr; Vol. 132 (4), pp. 801-805. Date of Electronic Publication: 2021 Aug 24.
DOI: 10.1002/lary.29833
Abstrakt: 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.
(© 2021 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)
Databáze: MEDLINE
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