title: Recurrences and second primary tumours in the head and neck region: differentiation by p53 mutation analysis.
abstract: BACKGROUND
  Patients with head and neck cancer are at high risk of developing additional primary tumours in the aerodigestive tract as a result of field cancerization phenomena. In this context, the appearance of a new neoplasm often poses a problem of differential diagnosis between recurrence and new primary tumour. The differentiation between the two entities in essentially clinical and conventionally based on the histological and spatio-temporal relations between the two lesions; however, the validity of these criteria has still to be assessed.
  
  
  METHODS
  To evaluate whether field cancerization phenomena may affect the clinical diagnosis of relapse/metastasis in the head and neck region, p53 mutation pattern was analysed in a series of primary tumours and corresponding recurrences/metastases. The rationale was that, since p53 mutations are a very early and polymorphic phenomenon, a recurrence/metastasis must retain the same mutation as the the primary tumour, whereas independent tumours are likely to display a different p53 gene status.
  
  
  RESULTS
  Molecular analysis provided conclusive results in 9 of 12 cases analysed. The clinical diagnosis of recurrence was confirmed by molecular analysis in 4 of these cases. In contrast, a differential p53 mutation pattern supported an independent origin for 3 presumed local recurrences and 2 lung lesions.
  
  
  CONCLUSIONS
  The use of p53 mutation analysis as a clonality marker allowed us to ascertain the inadequacy of the current diagnostic criteria for the differentiation between a new independent tumour and recurrence/metastasis. These findings substantiate the relevance of field cancerization phenomena in the head and neck region and prompt the use of p53 mutation analysis as a fundamental tool to improve the diagnosis and management of head and neck cancers.
authors.affiliation: Division of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Gasparotto
authors.forename: R
authors.initials: R
authors.lastname: Maestro
authors.forename: L
authors.initials: L
authors.lastname: Barzan
authors.forename: T
authors.initials: T
authors.lastname: Vukosavljevic
authors.forename: C
authors.initials: C
authors.lastname: Doglioni
authors.forename: S
authors.initials: S
authors.lastname: Sulfaro
authors.forename: S
authors.initials: S
authors.lastname: Piccinin
authors.forename: M
authors.initials: M
authors.lastname: Boiocchi
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D003937:Diagnosis, Differential; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014062:Tongue Neoplasms / Q000235:genetics / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm