Evaluation of DNA-Aneuploidy in Oral Cancer

Objectives: The aneuploidy-cancer theory proposes that cancer is caused by the abnormal dosage of thousands of normal genes. This is generated by the gain or loss of specific chromosomes or segments of chromosomes; alias aneuploidy. The theory predicts that chromosomal and genetic instability is proportional to the degree of aneuploidy (Duesberg et al., 2004). Therefore an abnormal DNA-Content of epithelial cells (alias the degrees of DNA-Aneuploidy) was determined by measuring the integrated optical density of abnormal keratinocytes using slide based DNA-Image-Cytometry (DNA-ICM). The aim of our prospective study was to investigate the diagnostic accuracy of DNA-ICM of minimal-invasive brush biopsies taken from suspicious oral lesions. Methods: Therefore we measured 480 smears of 1074 different lesions which were compared with histology and/or clinical follow-ups of the respective patients. Nuclear DNA contents were measured after Feulgen re-staining using a TV image analysis system. DNA-Aneuploidy was assumed if abnormal DNA-stemlines or cells with DNA-content greater 9c were observed. Results: On this basis the prevalence of DNA-aneuploidy in smears of oral squamous cell carcinomas in situ or invasive carcinomas was 98,4 %. Sensitivity of DNA-aneuploidy in oral smears for the detection of cancer cells was 98,40 % (95 % CI 95,38 – 99,67 %), specificity 99,34 % 98,40 % (95 % CI 97,64 – 99,92 %), positive predictive value 98,92 % (95 % CI 96,17 – 99,87 %) and negative 99,01 % (95 % CI 97,14 – 99,80 %). Conclusion: The appliance of DNA-ICM with DNA-aneuploidy as a marker for neoplastic transformation in oral smears secures cytologic diagnosis of carcinomas. DNA-Image-Cytometry is a very sensitive and highly specific, objective and reproducible adjuvant tool for identification of neoplastic cells in smears of oral brush biopsies.