The association between EGFR variant III, HPV, p16, c-MET, EGFR gene copy number and response to EGFR inhibitors in patients with recurrent or metastatic squamous cell carcinoma of the head and neck

Head Neck Oncol. 2011 Feb 27:3:11. doi: 10.1186/1758-3284-3-11.

Abstract

Background: We examine the potential prognostic and predictive roles of EGFR variant III mutation, EGFR gene copy number (GCN), human papillomavirus (HPV) infection, c-MET and p16INK4A protein expression in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Methods: We analyzed the archival tumor specimens of 53 patients who were treated in 4 phase II trials for R/M SCCHN. Two trials involved the EGFR inhibitor erlotinib, and 2 trials involved non-EGFR targeted agents. EGFRvIII mutation was determined by quantitative RT-PCR, HPV DNA by Linear Array Genotyping, p16 and c-MET protein expression by immunohistochemistry, and EGFR GCN by FISH.

Results: EGFRvIII mutation, detected in 22 patients (42%), was associated with better disease control, but no difference was seen between erlotinib-treated versus non-erlotinib treated patients. EGFRvIII was not associated with TTP or OS. The presence of HPV DNA (38%), p16 immunostaining (32%), c-MET high expression (58%) and EGFR amplification (27%), were not associated with response, TTP or OS.

Conclusion: EGFRvIII mutation, present in about 40% of SCCHN, appears to be an unexpected prognostic biomarker associated with better disease control in R/M SCCHN regardless of treatment with erlotinib. Larger prospective studies are required to validate its significance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Carcinoma / drug therapy
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / virology
  • Carcinoma, Squamous Cell
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor p16
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Gene Dosage
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / virology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / virology
  • Neoplasms, Squamous Cell / drug therapy
  • Neoplasms, Squamous Cell / genetics
  • Neoplasms, Squamous Cell / metabolism
  • Neoplasms, Squamous Cell / virology
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology
  • Prognosis
  • Proto-Oncogene Proteins c-met / biosynthesis*
  • Proto-Oncogene Proteins c-met / genetics
  • Squamous Cell Carcinoma of Head and Neck
  • Young Adult

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • epidermal growth factor receptor VIII
  • ErbB Receptors
  • Proto-Oncogene Proteins c-met