High-Frequency Targetable EGFR Mutations in Sinonasal Squamous Cell Carcinomas Arising from Inverted Sinonasal Papilloma

Cancer Res. 2015 Jul 1;75(13):2600-2606. doi: 10.1158/0008-5472.CAN-15-0340. Epub 2015 Apr 30.

Abstract

Inverted sinonasal papilloma (ISP) is a locally aggressive neoplasm associated with sinonasal squamous cell carcinoma (SNSCC) in 10% to 25% of cases. To date, no recurrent mutations have been identified in ISP or SNSCC. Using targeted next-generation sequencing and Sanger sequencing, we identified activating EGFR mutations in 88% of ISP and 77% of ISP-associated SNSCC. Identical EGFR genotypes were found in matched pairs of ISP and associated SNSCC, providing the first genetic evidence of a biologic link between these tumors. EGFR mutations were not identified in exophytic or oncocytic papillomas or non-ISP-associated SNSCC, suggesting that the ISP/SNSCC spectrum is biologically distinct among sinonasal squamous tumors. Patients with ISP harboring EGFR mutations also exhibited an increased progression-free survival compared with those with wild-type EGFR. Finally, treatment of ISP-associated carcinoma cells with irreversible EGFR inhibitors resulted in inactivation of EGFR signaling and growth inhibition. These findings implicate a prominent role for activating EGFR mutations in the pathogenesis of ISP and associated SNSCC and rationalize consideration of irreversible EGFR inhibitors in the therapy of these tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Sequence
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics*
  • Cell Line, Tumor
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Papilloma, Inverted / enzymology
  • Papilloma, Inverted / genetics*
  • Paranasal Sinus Neoplasms / enzymology
  • Paranasal Sinus Neoplasms / genetics*
  • Sequence Analysis, DNA
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • EGFR protein, human
  • ErbB Receptors