Abstract
The aim of this study was to investigate the relationship between tobacco smoke habit, patient age, DNA aneuploidy and genomic DNA copy number aberrations (CNAs) in oral potentially malignant disorder (OPMD) and oral squamous cell carcinoma (OSCC) patients. DNA aneuploidy was detected by high-resolution DNA flow cytometry (hr DNA-FCM) on DAPI stained nuclei obtained from multiple tissue samples from OPMDs/OSCCs in 220 consecutive patients. Nuclear genomic aberrations were determined in a subset of 65 patients by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. DNA aneuploidy and mean nuclear genomic aberrations were associated with patients’ age. In particular, DNA aneuploidy strongly associated with age in non-smoker OPMDs/OSCCs patients. OSCCs from smokers showed a lower prevalence of DNA aneuploidy compared to OSCCs from non-smokers. A higher occurrence of DNA aneuploidy (particularly in smokers’ OPMDs) was observed in patients characterized by involvement of a single oral subsite. Our study suggests that: 1) DNA aneuploidy in non-smokers is mainly related to aging; 2) OPMDs/OSCCs involving multiple oral subsites in smokers are less likely to develop DNA aneuploidy compared to non-smokers; 3) OSCC development is characterized by both CIN and CIN-independent mechanisms and that the latter are more relevant in smokers. This study provides evidence that DNA diploid OPMDs may be considered at lower risk of cancerization than DNA aneuploid ones in non-smokers but not in smokers.
Highlights
Oral potentially malignant disorders (OPMDs) are an heterogeneous group of asymptomatic mucosal alterations of various etiology associated to alteration of the nuclear genome that may lead to oral squamous cell carcinomas (OSCCs) [1]
When we examined the OPMDs/OSCCs from the non-smoker patients’ subgroup, the odds ratio (OR) of age increased to 1.12 (P
The present study shows for the first time a significant relationship between aging and DNA aneuploidy in OPMDs and between tobacco smoke and early appearance of DNA aneuploidy in OPMDs
Summary
Oral potentially malignant disorders (OPMDs) are an heterogeneous group of asymptomatic mucosal alterations of various etiology associated to alteration of the nuclear genome that may lead to oral squamous cell carcinomas (OSCCs) [1]. Several studies were conducted in an effort to find additional criteria that could predict the progression to OSCC of a given OPMD. Clinical studies showed that some subsites of the oral mucosa, which included tongue and floor of the mouth, have an increased risk of cancer development [5]. Further studies provided evidences of an association between DNA aneuploidy with high-risk oral mucosa subsites [12] and with genomic copy number aberrations [13]. The proof that DNA aneuploidy can predict the progression of given OPMD in a clinical setting is still missing and the same applies for some molecular markers, such as p53 (TP53), Cyclin D1, and podoplanin (PDPN), HIF-1alpha, E-cadherin, and p63, which were investigated [14, 15]
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