title: p53 mutations in deep tissues are more strongly associated with recurrence than mutation-positive mucosal margins.
abstract: OBJECTIVE
  Application of ultrasensitive diagnostics has shown that small numbers of p53 mutation-positive cells may signify the presence of residual tumor in histologically normal tissues after resection of squamous cell carcinomas arising in the head and neck area. To date, most studies in this area have focused on analysis of tissues at the mucosal aspect of the resection and highlighted the importance of molecular changes in the field with respect to the risk of recurrence.
  
  
  METHODS
  In the present investigation, we analyzed normal tissues from mucosal and deep surgical margins, referred to as "molecular margins," for the presence of the signature p53 mutation identified for each tumor.
  
  
  RESULTS
  The p53 mutation status of these carcinomas did not correlate with clinical or histopathologic variables, but these mutations provided an excellent target for ultrasensitive analysis of margin status. We found that 11 of 16 (68%) of cases with histologically tumor-free (including 9 without dysplasia), but with p53 mutation-positive molecular margins, developed recurrence. The probability of developing local recurrence was significantly higher for the group with p53 mutation-positive margins when compared with the group with clear margins (P = 0.048) and more strongly associated with p53 mutation-positive deep molecular margins than mutation-positive mucosal molecular margins or positivity at both sites (P = 0.009).
  
  
  CONCLUSIONS
  This shows that although persistent mucosal fields may contribute to recurrence, clonal p53 mutations in deep tissues are an important cause of treatment failure, and molecular margins from both sites should be analyzed in future prospective series.
authors.affiliation: Maxillofacial Surgery, King's College Hospital, London, United Kingdom.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Huang
authors.forename: Stelios
authors.initials: S
authors.lastname: Pateromichelakis
authors.forename: Allison
authors.initials: A
authors.lastname: Hills
authors.forename: Martyn
authors.initials: M
authors.lastname: Sherriff
authors.forename: Andrew
authors.initials: A
authors.lastname: Lyons
authors.forename: John
authors.initials: J
authors.lastname: Langdon
authors.forename: Edward
authors.initials: E
authors.lastname: Odell
authors.forename: Peter
authors.initials: P
authors.lastname: Morgan
authors.forename: John
authors.initials: J
authors.lastname: Harrison
authors.forename: Max
authors.initials: M
authors.lastname: Partridge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism*; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D011237:Predictive Value of Tests; D012008:Recurrence; D012680:Sensitivity and Specificity