Abstract 641: Correlation of methylation status of deep surgical margins with the local reccurence of head and neck squamous cell carcinoma.

Abstract

Abstract Background: Locoregional recurrence occurs in as many as 40% of patients undergoing surgery for head and neck squamous cell carcinoma (HNSCC). We have been focused some molecular alterations exsiting even in histologically negative surgical margins. However, in head and neck cancer resection, surgical margins are hard to evaluate because the most of them usually consists of complicated muscular margins. In order to evaluate these deep surgical margins, before collecting some margin tissues, we often conduct tissue imprinting by using one layer nitrocellulose sheet which can collect proteins without hurting surgical samples. Method: Both 161 deep margin tissues and 166 deep margin imprints were collected from 74 histologically margin negative resections of primary HNSCC from May, 2009 to September, 2012. Bisulfited DNA from samples were amplified using quantitive methylation-specific polymerase chain reaction (QMSP) for 6 genes (DCC, EDNRB, HOXA9, KIF1A, NID2 and NR2B). The cut off value was calculated using QMSP data of tumors and normal muscles, and was applied to deep margin samples. The correlation between the QMSP status of deep margin samples and clinical outcome was evaluated. Results: The average QMSP of tumor tissues, that of normal muscles and the cut off value are 21.0, 0.6, 2.1 in DCC, 23.3, 0.6, 2.2 in EDNRB, 32.0, 0.7, 2.3 in HOXA9, 20.3, 0.4, 1.3 in KIF1A, 36.0, 3.0, 9.4 in NID2 and 10.7, 0.1, 0.4 in NR2B. Those who has the higher QMSP values of deep margin tissues than the cut off value tends to have a poor recurrence free survival (P=0.073 in DCC, P=0.018 in HOXA9, P=0.005 in KIF1A, P=0.011 in NID2) and a poor overall survival (P=0.076 in HOXA9, P=0.059 in NID2). Also, those who has the higher QMSP values of deep margin imprints than the cut off value tends to have a poor recurrence free survival (P=0.051 in HOXA9) and a poor overall survival (P=0.075 in HOXA9). Conclusion: The methylation status of HNSCC deep surgical margin samples is correlated with the local recurrence. Especially, hyper-methylated HOXA9 gene of both deep margin tissues and imprints is a significant biomarker of poor recurrence free survival and overall survival. Citation Format: Masamichi Hayashi, Gaosong Wu, Xiaofei Chang, Xiufeng Li, Julie Ahn, Zubair Khan, Belinda Akpeng, Jong–Lyel Roh, Wayne Koch. Correlation of methylation status of deep surgical margins with the local reccurence of head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 641. doi:10.1158/1538-7445.AM2013-641