title: EGFR and K-ras gene mutation status in squamous cell anal carcinoma: a role for concurrent radiation and EGFR inhibitors?
abstract: BACKGROUND
  There is a growing appreciation for radio-sensitiser use in multi-modal cancer treatment models. Squamous cell anal carcinoma (SCAC) is a rare gastrointestinal tumour traditionally treated with concurrent chemotherapy and radiation. Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, has demonstrated significant efficacy when combined with radiation in squamous cell carcinoma of the head and neck (SccH&N). We wanted to assess EGFR and Kirsten-ras (K-ras) status in SCAC to see whether it compares with SccH&N.
  
  
  METHODS
  Over 90 SCAC paraffin-embedded biopsies were mounted onto a tissue microarray and were assessed for EGFR expression by immunohistochemistry. These samples were also assessed for the most frequently mutated K-ras and EGFR exons by high-resolution melting analysis.
  
  
  RESULTS
  The EGFR was present in over 90% of samples tested. The K-ras and EGFR mutations were absent in all samples tested, although a synonymous single-nucleotide polymorphism was found in 3 out of 89 samples tested for EGFR exon 19.
  
  
  CONCLUSIONS
  The low rate of K-ras and EGFR mutations, coupled with the high surface expression of EGFR, suggests similarity in the EGFR signalling pathway between SCAC and SccH&N, and thus a potential role for EGFR inhibitors in SCAC. To our knowledge this is the largest cohort of invasive SCAC samples investigated for EGFR and K-ras mutations reported to date.
authors.affiliation: Faculty of Medicine, McGill University, Montreal, Quebec, Canada H3G 1Y6. aleks.p@gmail.com
authors.forename: A
authors.initials: A
authors.lastname: Paliga
authors.forename: R
authors.initials: R
authors.lastname: Onerheim
authors.forename: A
authors.initials: A
authors.lastname: Gologan
authors.forename: G
authors.initials: G
authors.lastname: Chong
authors.forename: A
authors.initials: A
authors.lastname: Spatz
authors.forename: T
authors.initials: T
authors.lastname: Niazi
authors.forename: A
authors.initials: A
authors.lastname: Garant
authors.forename: D
authors.initials: D
authors.lastname: Macheto
authors.forename: T
authors.initials: T
authors.lastname: Alcindor
authors.forename: T
authors.initials: T
authors.lastname: Vuong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000235:genetics* / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy; D059248:Chemoradiotherapy; D066246:ErbB Receptors / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics*; D005091:Exons; D005260:Female; D006258:Head and Neck Neoplasms; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D000077195:Squamous Cell Carcinoma of Head and Neck; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins