Wednesday, August 25, 2021

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

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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, 2021

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