title: Correlation of Ataxia-Telangiectasia-Mutated (ATM) gene loss with outcome in head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  Ataxia-Telangiectasia-Mutated (ATM) gene loss has been associated with poor prognosis and treatment resistance in head and neck squamous cell carcinomas (HNSCC). We investigated the relationship between ATM loss detected by fluorescence in-situ hybridisation (FISH) with patient outcome, and its relationship with Human Papillomavirus (HPV)/p16(INK4A) status.
  
  
  METHODS
  Copy number of the ATM gene and chromosome 11 were determined by FISH and HPV status was determined using p16(INK4A) immunohistochemistry in 87 paraffin embedded tumour samples from patients with HNSCC treated with chemoradiation at a single institution. ATM loss was correlated with patient outcome as both a continuous and dichotomous variable.
  
  
  RESULTS
  Of 73 evaluable patients, 44 (60.3%) demonstrated loss of the ATM gene. There was no correlation between ATM loss (defined as a mean ratio of ATM: chromosome 11<0.75) and overall survival (OS, p=0.67) or time to locoregional failure (TTLRF, p=0.72). Similarly, when evaluated as a continuous variable there was no significant relationship between ATM loss and patient outcome (OS, p=0.89; TTLRF, p=0.21). No significant relationship was found between p16(INK4A) status and ATM loss, for patient outcome. We found 35.6% (n=26) of patients demonstrated polysomy of chromosome 11 (defined as the presence of a mean >2.5 copies of chromosome 11) which was significantly associated with p16(INK4A) negative status (p=0.0004), but did not influence outcome.
  
  
  CONCLUSIONS
  ATM loss is a frequent event in HNSCC, however it does not impact outcome after treatment with chemoradiation. Polysomy of chromosome 11 was significantly associated with p16(INK4A) negative status but also lacks prognostic significance.
authors.affiliation: Department of Medical Oncology, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Lim
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Young
authors.forename: Marnie
authors.initials: M
authors.lastname: Collins
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fox
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
authors.forename: June
authors.initials: J
authors.lastname: Corry
authors.forename: Lester
authors.initials: L
authors.lastname: Peters
authors.forename: Danny
authors.initials: D
authors.lastname: Rischin
authors.forename: Benjamin
authors.initials: B
authors.lastname: Solomon
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000628:therapy; D016896:Treatment Outcome