title: Microenvironmental genomic alterations and clinicopathological behavior in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Carcinogens associated with head and neck squamous cell carcinoma (SCC) genesis should inflict genomic alterations not only on the epithelium but also the mesenchyme of the aerodigestive tract. Therefore, the apparently nonmalignant stroma surrounding the tumor epithelium can acquire genomic alterations and contribute to cancer initiation and progression.
  
  
  OBJECTIVE
  To determine compartment-specific loci of loss of heterozygosity or allelic imbalance (LOH/AI) and to identify which genomic alterations restricted to the stroma cell population contribute to aggressiveness of head and neck SCC disease.
  
  
  METHODS
  Tumor epithelium and surrounding stroma were isolated from 122 US patients with oral cavity and oropharyngeal or hypopharyngeal SCC and subjected to whole-genome LOH/AI analysis using 366 microsatellite markers. Samples, collected between 2001 and 2004, were pulled and transferred in batches of 10 to 30 between 2002 and 2005. Laser capture microdissection DNA extraction and technical genotyping occurred on a rolling model between 2002 and November 2005.
  
  
  METHODS
  Compartment-specific frequency and distribution of LOH/AI were determined, and hot spots of genomic alterations identified. Compartment-specific LOH/AI events were correlated with presenting clinicopathologic characteristics.
  
  
  RESULTS
  Tumor-associated stroma of head and neck SCC from smokers were found to have a high degree of genomic alterations. A correlation between tumor aggressiveness could be found for a specific set of 5 loci. Three stroma-specific loci (D4S2417, D3S360, and D19555) were associated with tumor size (pT) and regional nodal metastases (pN). Furthermore, 2 epithelial-specific LOH/AI hot spots were positively correlated with pN status and clinical stage.
  
  
  CONCLUSIONS
  Stroma-specific genetic alterations are associated with smoking-related head and neck SCC genesis. These findings suggest novel prognostic or diagnostic biomarkers and identify potential new molecular targets for therapeutic and preventive intervention.
authors.affiliation: Genomic Medicine Institute and Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Weber
authors.forename: Yaomin
authors.initials: Y
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Attila
authors.initials: A
authors.lastname: Patocs
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.forename: Petra
authors.initials: P
authors.lastname: Platzer
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
mesh_terms: D000368:Aged; D022981:Allelic Imbalance; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004273:DNA, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D010610:Pharyngeal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D012907:Smoking / Q000009:adverse effects
chemical_list: D002273:Carcinogens; D004273:DNA, Neoplasm