Background
Securing negative surgical margins is a critical goal for head and neck surgery. Local recurrence occurs even in some cases with histologically negative surgical margins. Minimal residual tumor cells may lead to locoregional recurrence despite clear histologic margins reported at the time of resection of head and neck squamous cell carcinoma (HNSCC). In order to identify subclinical residual disease, we analyzed deep margin imprint samples collected on one layer nitrocellulose sheets.
Methods
Bisulfite treated DNA from 73 eligible cases was amplified by quantitative methylation-specific polymerase chain reaction (QMSP) targeting 6 genes (DCC, EDNRB, HOXA9, KIF1A, NID2, NR2B). QMSP values were dichotomized as positive or negative. Associations between the QMSP status of deep margin samples and clinical outcomes were evaluated.
Results
Two gene methylation combinations among DCC, EDNRB and HOXA9 were associated with decreased locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS). The methylated gene combination EDNRB and HOXA9 in margin imprints was the most powerful predictor of poor LRFS (HR=3.31, 95% CI=1.30-8.46; P=0.012), independent of standard histological factors. In addition, methylation of EDNRB/HOXA9 showed a trend toward reduced RFS (HR=2.74, 95% CI=0.90-8.33; P=0.075) and OS (HR=5.78, 95% CI=0.75-44.7; P=0.093) by multivariable analysis.
Conclusion
A panel of gene methylation targets in deep surgical margin imprints provides a potential predictive marker of post-operative locoregional recurrence. Intra-operative use of molecular margin-imprint analysis might assist surgeons to obtain rigorously negative surgical margins and improve the outcome of head and neck surgery.
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