title: Genetic characterization of vocal fold lesions: leukoplakia and carcinoma.
abstract: OBJECTIVE
  Malignant transformation of laryngeal keratosis has been reported in a substantial subset of patients, yet reliable criteria for predicting patients most at risk have yet to be determined. Current methods for determining dysplasia ratings are susceptible to errors in biopsy sampling and interpretation. An understanding of the genetic underpinnings of the progression of vocal fold tumorigenesis may contribute to the creation of reliable and predictive diagnostic criteria. We hypothesized that genetic expression markers distinguish patients with keratotic noncancerous vocal fold lesions from invasive carcinoma.
  
  
  METHODS
  Observational cross-sectional study.
  
  
  METHODS
  Real-time polymerase chain reaction (RT-PCR) was used to compare expression of 84 cancer pathway genes of patients following histologic diagnosis of nondysplastic keratotic epithelium (ND) (n = 7), dysplastic keratotic epithelium (DYS) (n = 3), and invasive carcinoma (CA) (n = 7). All patients had a clinical diagnosis of leukoplakia, and biopsies were obtained from true vocal fold tissue.
  
  
  RESULTS
  Four genes (IGF-1, EPDR1, MMP-2, S100A4) were significantly upregulated in DYS over the ND group. Seven genes were significantly upregulated in CA over the DYS group, and 31 genes were significantly upregulated in CA over the ND group (P < .02). The expression of matrix metalloproteinases (MMP-1, MMP-2, MMP-9) was found to statistically differentiate the groups (P < .02) and suggested disease progression associated with extracellular matrix degradation and angiogenesis promotion.
  
  
  CONCLUSIONS
  With these preliminary array data, we demonstrate the feasibility of using RT-PCR to identify distinct genetic expression between diagnostic groups. Characterization of genetic changes marking the progression of vocal fold tumorigenesis may lead to robust diagnostic criteria in the future.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, University of Wisconsin-Madison, Madison, Wisconsin 53792, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Bartlett
authors.forename: W Wesley
authors.initials: WW
authors.lastname: Heckman
authors.forename: Jason
authors.initials: J
authors.lastname: Isenberg
authors.forename: Susan L
authors.initials: SL
authors.lastname: Thibeault
authors.forename: Seth H
authors.initials: SH
authors.lastname: Dailey
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics*; D003430:Cross-Sectional Studies; D004273:DNA, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D007971:Leukoplakia / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D014827:Vocal Cords / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm