This project was completed at the University of Wisconsin–Madison.
Version of Record online: 17 JAN 2012
Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.
Volume 122, Issue 2, pages 336–342, February 2012
How to Cite
Bartlett, R. S., Heckman, W. W., Isenberg, J., Thibeault, S. L. and Dailey, S. H. (2012), Genetic characterization of vocal fold lesions: Leukoplakia and Carcinoma. The Laryngoscope, 122: 336–342. doi: 10.1002/lary.22417
This work was supported by the University of Wisconsin–Madison Division of Otolaryngology Resident Education Fund and the National Institute of Deafness and Other Communication Disorders (R01 DC009600). The authors have no other funding, financial relationships, or conflicts of interest to disclose.
- Issue online: 23 JAN 2012
- Version of Record online: 17 JAN 2012
- Manuscript Accepted: 2 AUG 2011
- Manuscript Revised: 27 JUL 2011
- Manuscript Received: 1 MAR 2011
- vocal fold tumorigenesis;
- genetic expression;
- laryngeal keratosis;
- Level of Evidence: 4
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.
Observational cross-sectional study.
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.
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.
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.