title: Chromosomal aneuploidy precedes morphological changes and supports multifocality in head and neck lesions.
abstract: OBJECTIVE
  To identify chromosome changes associated with the transformation of dysplastic lesions and to verify evidence for multifocality in synchronous premalignant lesions associated with head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Chromosomal aneuploidy was evaluated in sections of formalin-fixed, paraffin-embedded tissues from 16 patients with HNSCC, including sites with normal squamous mucosa, dysplasia (low- and high-grade), and invasive tumor.
  
  
  METHODS
  A panel of 6 centromeric probes (chromosomes 1, 3, 7, 8, 9, and 17) was analyzed in dual-color fluorescence in situ hybridization assays, using matched hematoxylin-eosin-stained sections for histologic correlation.
  
  
  RESULTS
  Imbalances for most of the targets tested were found in 20 of 24 invasive carcinoma sites, mainly represented by gain in copy number per cell. However, cell populations with chromosome losses and gains in multimodal patterns were concomitantly observed in a number of tumors, indicating a high degree of chromosome instability. The detection of chromosomal aneuploidy precedes the malignant transformation as indicated by findings of monosomy and trisomy in normal squamous mucosa, and in low-grade and high-grade dysplasia sites. Loss of chromosomes 3 and 17 prevailed in low-grade dysplasias, and gain of chromosomes 7 and 8 were prevalent in high-grade dysplasias. Synchronous low-grade and high-grade dysplastic lesions displayed discordant molecular signatures, suggesting a multifocal origin.
  
  
  CONCLUSIONS
  The interphase fluorescence in-situ hybridization (FISH) assay with centromeric may detect early changes in the progression of dyplastic epithelia to invasive carcinoma and supports the field cancerization theory of multifocality.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA.
authors.forename: H
authors.initials: H
authors.lastname: Ai
authors.forename: J E
authors.initials: JE
authors.lastname: Barrera
authors.forename: A D
authors.initials: AD
authors.lastname: Meyers
authors.forename: K R
authors.initials: KR
authors.lastname: Shroyer
authors.forename: M
authors.initials: M
authors.lastname: Varella-Garcia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D010039:Otorhinolaryngologic Neoplasms / Q000235:genetics* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology