Molecular screening of oral precancer

• Published in: Oral oncology Vol. 49; no. 12; pp. 1129 - 1135
• Main Authors: Graveland, A. Peggy, Bremmer, Jantine F, de Maaker, Michiel, Brink, Arjen, Cobussen, Paul, Zwart, Meindert, Braakhuis, Boudewijn J.M, Bloemena, Elisabeth, van der Waal, Isaäc, Leemans, C. René, Brakenhoff, Ruud H
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.12.2013; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Early Detection of Cancer - methods; Female; Genetic Markers; Hematology, Oncology and Palliative Medicine; Humans; Leukoplakia; Leukoplakia, Oral - genetics; Leukoplakia, Oral - pathology; Loss of heterozygosity; Male; Malignant transformation; Mass Screening - methods; Medical sciences; Microsatellite Repeats; Middle Aged; Molecular diagnosis; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Oral cancer; Otolaryngology; Otorhinolaryngology. Stomatology; p53; Premalignant oral lesions; Risk Factors; Screening; Sensitivity and Specificity; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Screening; Molecular diagnosis; Oral cancer; Malignant transformation; Loss of heterozygosity; Premalignant oral lesions; Leukoplakia; p53; Premalignant lesion; Stomatology; Oral administration; ENT; Malignant tumor; Medical screening; Heterozygosity; Cancerology; Leukoplasia; Oral cavity disease; Diagnosis; Cancer
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2013.09.005

Summary Objectives 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. Materials and 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). Conclusion 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.