Association Between Hypermethylated Tumor and Paired Surgical Margins in Head and Neck Squamous Cell Carcinomas

Abstract

Purpose: Surgical margin status is reported to be a relevant prognostic factor in head and neck squamous cell carcinoma (HNSCC), associated with a high risk of local recurrence. This study examines whether gene-promoter hypermethylation could be detected in HNSCC surgical margins with no histologic evidence of malignancy, and if so, whether it reflects epigenetic events of primary tumors. Experimental Design: Promoter methylation status of MGMT, p16, and DAP-K genes was evaluated by methylation-specific PCR in 20 primary HNSCC tumors. Histopathologically negative surgical margins of hypermethylated tumors were collected, and their methylation status compared with the primary tumor status. Results: Promoter hypermethylation in at least one of the three tested genes was detected in 65% (13 of 20) of tumors. MGMT was hypermethylated in 50% (10 of 20), DAP-K in 45% (9 of 20), and p16 in 20% (4 of 20) of tumors. Methylation status was analyzed in 35 margins from 11 of 13 patients showing promoter hypermethylation in the tumor tissue. Identical methylation events were seen for at least one gene in primary tumor and surgical margins in 9 of 11 cases (82%). Association was found for gene-specific hypermethylation status in tumors and paired surgical margins, and gene-specific concordance was 63% for MGMT (j = 0.24), 90% for DAP-K (j = 0.74), and 90% for p16 (j = 0.79). Conclusions: Our results support the hypothesis that detection of gene promoter hypermethylation in HNSCC tumor cells^free surgical margins may be a helpful biomarker to identify molecularly altered fields in areas adjacent to the tumor.

Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma

“…The results include MGMT hypermethylation, which has been previously described in several studies, thus adding plausibility to our screening results. 12,13 Information about epigenetic regulation of SALL3 and FANCB in cancer is rather rare. 20,21 MSH4 was recently shown to be hypermethylated in HNSCC.…”

Hypermethylation of collagen α2 (I) gene (COL1A2) is an independent predictor of survival in head and neck cancer

“…The PCR products were 82 bp long. To analyze the methylation status of the p16 gene [5], E-cadherin gene [6], RASSF1A gene [7], H-cadherin gene [22], DAPK gene [23], MGMT gene [23], and DCC gene [24], primers and conditions as described previously were used. The PCR products were separated by electrophoresis through a 9% polyacrylamide gel and stained with ethidium bromide.…”

Epigenetics in Head and Neck Squamous Cell Carcinoma

“…The epigenetic field defect was observed for oesophageal (Oka et al, 2009), lung (Guo et al, 2004) or stomach (Ushijima, 2007) cancers. Similarly, epigenetic www.intechopen.com changes in normal mucosa cells derived from surgical margins were detected in head and neck carcinomas (Martone et al, 2007). However, so far such changes have not been observed specifically in laryngeal cancers.…”