title: Mutation analysis of genes in the EGFR pathway in Head and Neck cancer patients: implications for anti-EGFR treatment response.
abstract: BACKGROUND
  Targeted therapy against the Epidermal Growth Factor Receptor (EGFR) is among the most promising molecular therapeutics for Head and Neck Squamous Cell Carcinoma (HNSCC). However, drug resistance limits the clinical efficacy of anti-EGFR monoclonal antibodies and no predictive biomarker has entered the clinic yet.
  
  
  METHODS
  A retrospective clinical study was performed utilizing pathological specimens from 52 newly diagnosed HNSCC patients. These patients were screened for mutations in EGFR and KRAS. Tyrosine kinase mutations in EGFR and KRAS mutations were evaluated by high resolution melting analysis (HRMA), whereas EGFRvIII was determined using one-step real-time PCR. Finally, patient samples were screened for HPV-DNA by GP5+/6+ PCR. Survival analysis was performed using Kaplan-Meier analysis and significance was calculated using log-rank statistic.
  
  
  RESULTS
  In our study population no EGFRvIII mutations were present. However, two silent mutations were found; T785T in exon 20 and R836R in exon 21 of the EGFR gene. Additionally, HRMA revealed an abnormal KRAS melting pattern in 7.0% of the samples. However, the KRAS StripAssay could confirm only one sample with a G12S mutation and none of these samples could be confirmed by direct sequencing. HPV DNA was present in 3/25 larynx and 9/27 oropharynx tumors.
  
  
  CONCLUSIONS
  The low rate of EGFR and KRAS mutations in this Belgian HNSCC population suggests that these genes will probably not play a major role in predicting response to anti-EGFR therapy in HNSCC. Hence, other predictive markers need to be discovered in order to optimize EGFR targeting therapy.
authors.affiliation: Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Wilrijk, Belgium. carolien.boeckx@uantwerpen.be.
authors.forename: Carolien
authors.initials: C
authors.lastname: Boeckx
authors.forename: Christine
authors.initials: C
authors.lastname: Weyn
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vanden Bempt
authors.forename: Vanessa
authors.initials: V
authors.lastname: Deschoolmeester
authors.forename: An
authors.initials: A
authors.lastname: Wouters
authors.forename: Pol
authors.initials: P
authors.lastname: Specenier
authors.forename: Carl
authors.initials: C
authors.lastname: Van Laer
authors.forename: Danielle
authors.initials: D
authors.lastname: Van den Weyngaert
authors.forename: Mark
authors.initials: M
authors.lastname: Kockx
authors.forename: Jan B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.forename: Filip
authors.initials: F
authors.lastname: Lardon
authors.forename: Marc
authors.initials: M
authors.lastname: Baay
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D017931:DNA Primers; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; D066246:ErbB Receptors