Chromosomal aberrations and aneuploidy in oral potentially malignant lesions: distinctive features for tongue

Abstract

Background: The mucosae of the oral cavity are different at the histological level but appear all equally exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia may develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs) in the OPMLs from different oral anatomical subsites.

Methods: Samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on DNA obtained from diploid nuclei suspensions directly. When aneuploid nuclei were detected, these were physically separated from diploid nuclei on the base of their DI values by means of a DNA-FCM-Sorter in order to improve the a-CGH analysis.

Results: Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites.

Conclusions: We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this hypothesis should be validated in a prospective clinical study.

Figure 1

Percentage of DNA aneuploid tissue samples, as determined by high resolution DNA flow cytometry (hr DNA-FCM), found in the tongue and in all the other anatomical oral mucosa subsites for Oral Distant Fields (ODFs), non-dysplastic and dysplastic Oral Potentially Malignant Lesions (nd-OPMLs and d-OPMLs, respectively). OR, odd ratio. The numerical data are shown in Tables 3 and 4. Standard errors for each data point are shown as vertical bars.

Figure 2

Total gains of CNAs (see Material and Methods for details) of the tongue Oral Potentially Malignant Lesions (OPMLs) or of OPMLs from all the other anatomical mucosa subsites. The values ranged from 0 (no DNA copy gains) to 41 (one or more gains found in each one of the investigated chromosomal arms). (A) Unstratified data. (B) Data stratified for DNA aneuploidy. The number of samples in each group is shown. Each box represented the median and the first and third quartiles, and the whiskers extended as far as the minimum and maximum values after exclusion of the outliers (values more than 1.5 interquartile ranges below the lower quartile or above the upper quartile). Excluded outliers (with value less than 3 interquartile ranges outside the first and third quartiles) were displayed as circles.