title: Molecular screening of oral precancer.
abstract: OBJECTIVE
  Early detection and treatment of high risk premalignant mucosal changes of the oral cavity, will expectedly improve survival and reduce treatment-related morbidity. Aims of this study were to evaluate a non-invasive screening approach and to assess the value of molecular markers to identify patients at risk for oral cancer.
  
  
  METHODS
  Exfoliated cells and biopsies were obtained from oral leukoplakia lesions of 43 patients, of whom six developed oral cancer. All samples were investigated for loss of heterozygosity (LOH) at chromosomes 3p, 9p, 11q and 17p using microsatellite markers. On the biopsy specimen additional immunohistochemical staining for p53, TP53 mutation analysis and histopathological grading were performed.
  
  
  RESULTS
  The analytical sensitivity of the non-invasive assay using exfoliated cells to detect genetic changes present in the lesions was 45% (9 of 20), the specificity was 100% (19 of 19), and the positive predictive value was also 100% (9 of 9). LOH was present in 20 of 39 (51%) of the biopsies with uniformly LOH at 9p. Mutated TP53 and LOH at 9p in the biopsy, as single markers and in combination, were significant risk factors for malignant progression of leukoplakia to oral cancer (Kaplan-Meier analysis, p<0.05).
  
  
  CONCLUSIONS
  A non-invasive genetic screening approach using LOH in exfoliated cells has limited value for monitoring patients with leukoplakia. However, LOH at 9p, but also mutated TP53 in biopsies of oral leukoplakia have a significant association with malignant transformation and are promising candidate biomarkers to predict the risk for malignant progression.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: ap.graveland@vumc.nl.
authors.forename: A Peggy
authors.initials: AP
authors.lastname: Graveland
authors.forename: Jantine F
authors.initials: JF
authors.lastname: Bremmer
authors.forename: Michiel
authors.initials: M
authors.lastname: de Maaker
authors.forename: Arjen
authors.initials: A
authors.lastname: Brink
authors.forename: Paul
authors.initials: P
authors.lastname: Cobussen
authors.forename: Meindert
authors.initials: M
authors.lastname: Zwart
authors.forename: Boudewijn J M
authors.initials: BJ
authors.lastname: Braakhuis
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bloemena
authors.forename: Isaäc
authors.initials: I
authors.lastname: van der Waal
authors.forename: C René
authors.initials: CR
authors.lastname: Leemans
authors.forename: Ruud H
authors.initials: RH
authors.lastname: Brakenhoff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007972:Leukoplakia, Oral / Q000235:genetics / Q000473:pathology; D008297:Male; D008403:Mass Screening / Q000379:methods*; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D005819:Genetic Markers
keywords: Leukoplakia; Loss of heterozygosity; Malignant transformation; Molecular diagnosis; Oral cancer; Premalignant oral lesions; Screening; p53