title: The origins of multiple squamous cell carcinomas in the aerodigestive tract.
abstract: BACKGROUND
  Chemoprevention and cessation of smoking and alcohol may prevent development of multiple tumors (MTs) in the aerodigestive tract if new MTs arise independently, but they are of no benefit if MTs are due to migration of an already transformed clone of tumor cells. This issue was addressed in this study by investigation of the clonality among MTs.
  
  
  METHODS
  Mutation analysis of the entire coding region of p53 and loss of heterozygosity (LOH) pattern analysis of microsatellite markers on chromosome arms 3p, 9p, and 17p are promising for the investigation of clonality. In the first part of this study, the authors established the variability and stability of these clonal markers by comparing primary head and neck squamous cell carcinomas (HNSCCs) with their metastases. In the second part of this study, the authors evaluated nine patients with multiple HNSCCs using these markers. In the final part, the authors illustrate the use of these clonal markers in 11 patients for whom there was diagnostic uncertainty as to whether their second squamous cell carcinoma was either a new primary tumor, a metastasis, or a recurrence.
  
  
  RESULTS
  Both p53 gene mutations and LOH patterns were stable during tumor progression. Furthermore, the variability of p53 gene mutations was high. More than 90% of the tumors contained a p53 mutation. A particular mutation never occurred more than twice in a total of 69 primary HNSCCs. Five of 69 cases presented a common mutation. In contrast, LOH patterns showed less variability; they were identical in 5 of 16 cases. The metachronous HNSCCs from nine patients all showed different p53 mutations, and in the three cases that were subjected to LOH analysis different patterns were observed. All 11 patients for whom there was diagnostic uncertainty about the origin of their second squamous cell carcinoma could be categorized as having multiple primary tumors, disseminated disease, or recurrent disease.
  
  
  CONCLUSIONS
  Metachronous HNSCCs at different locations are not clonally related and thus have not developed from the migration of tumor cells.
authors.affiliation: Department of Pathology, University Medical Center, Utrecht, The Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: van Oijen
authors.forename: F G
authors.initials: FG
authors.lastname: Leppers Vd Straat
authors.forename: M G
authors.initials: MG
authors.lastname: Tilanus
authors.forename: P J
authors.initials: PJ
authors.lastname: Slootweg
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D002999:Clone Cells; D016158:Genes, p53 / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009062:Mouth Neoplasms / Q000235:genetics; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000235:genetics*; D010039:Otorhinolaryngologic Neoplasms / Q000235:genetics