Gene Methylation Profiling in Sinonasal Adenocarcinoma and Squamous Cell Carcinoma

Otolaryngol Head Neck Surg. 2016 Nov;155(5):808-815. doi: 10.1177/0194599816654139. Epub 2016 Jun 14.


Objective: To identify epigenetic events in intestinal-type sinonasal adenocarcinoma (ITAC) and sinonasal squamous cell carcinoma (SNSCC) and to evaluate their relation to clinicopathologic features and follow-up data.

Study design: Retrospective study.

Setting: Academic research hospital.

Subjects and methods: The methylation status of 23 genes in 50 ITACs and 32 SNSCCs was analyzed by methylation-specific multiplex ligation-dependent probe amplification and its relation to clinicopathologic features and follow-up data.

Results: Gene methylation was observed in 50% of all tumors. Recurrent methylated genes in SNSCC were RASSF1 and CDH13 (for both, 6 of 32 cases), CHFR (4 of 32 cases), and TIMP3 (2 of 32 cases). None of these genes showed significant correlation to clinicopathologic features or overall survival. In ITAC, recurrent methylated genes were CDH13 (18 of 50 cases), ESR1 (13 of 50 cases), APC (7 of 50 cases), TIMP3 (5 of 50 cases), CASP8 (3 of 50 cases), and HIC1 and RASSF1 (for both, 2 of 50 cases). Papillary and colonic ITAC subtypes carried a mean of 1.26 gene methylations per tumor versus 0.63 in solid and mucinous subtypes. Methylation of TIMP3 was associated with a significantly worse survival in ITAC patients.

Conclusion: ITAC carries a higher number and a different profile of gene methylations as compared with SNSCC. Gene methylation plays a greater role in papillary and colonic ITAC subtypes, which may indicate a different tumorigenic pathway for these ITAC subtypes. These findings could be used as prognosticators and may have implications for future individualized therapies based on epigenetic changes.

Keywords: adenocarcinoma; gene methylation; prognosis; sinonasal cavities; squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • DNA Methylation*
  • DNA Mutational Analysis / methods*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiplex Polymerase Chain Reaction / methods*
  • Neoplasm Staging
  • Paranasal Sinus Neoplasms / genetics*
  • Paranasal Sinus Neoplasms / pathology
  • Paranasal Sinus Neoplasms / therapy
  • Prognosis
  • Retrospective Studies
  • Survival Rate


  • Biomarkers, Tumor