Detection of EGFR- and HER2-activating mutations in squamous cell carcinoma involving the head and neck

Mod Pathol. 2006 May;19(5):634-40. doi: 10.1038/modpathol.3800552.


Recent reports have indicated that mutations in the epidermal growth factor receptor-1 (EGFR) occur in about 7% of patients with squamous cell carcinoma of the head and neck. It is known that many patients with non-small-cell lung cancer who respond to the EGFR inhibitors gefitinib and erlotinib have tumors with EGFR-activating mutations. This might suggest that patients with head and neck squamous carcinoma, who also have tumors with EGFR-activating mutations, might represent a patient population who could benefit from gefitinib or erlotinib therapy. High-resolution melting amplicon analysis (HRMAA) is a recently described technique which can be used for screening tumor DNA isolated from paraffin blocks for tyrosine kinase-activating mutations. In this report we screened 24 cases of squamous cell carcinoma, either primary in the head and neck or secondarily involving the head and neck area, for activating mutations in EGFR exons 18, 19, 20, 21, and for HER2 exons 19 and 20. All cases were followed up by direct DNA sequencing. Two (8%) of the 24 cases were positive. One case was a maxillary sinus tumor which contained an exon 20-activating mutation (N771YinsG). Surprisingly, the other case was a primary squamous cell carcinoma of the skin which invaded the head and neck area only secondarily. This tumor contained an exon 19-activating mutation (G729E). No HER2-activating mutations were found. The presence of a small number of squamous cell carcinomas in the head and neck area with EGFR-activating mutations suggests the existence of a population of patients who could derive benefit from gefitinib or erlotinib therapy. HRMAA could serve as a screening method to easily and rapidly identify these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • DNA Mutational Analysis / methods
  • DNA, Neoplasm / chemistry
  • DNA, Neoplasm / genetics
  • ErbB Receptors / genetics*
  • Female
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Nucleic Acid Amplification Techniques / methods
  • Nucleic Acid Conformation
  • Receptor, ErbB-2 / genetics*
  • Reproducibility of Results


  • DNA, Neoplasm
  • ErbB Receptors
  • Receptor, ErbB-2