Oral potentially malignant lesions (OPMLs) with dysplasia and
aneuploidy are thought to have a high risk of progression into
oral squamous cell carcinomas (OSCCs). Non-dysplastic "oral distant fields" (ODFs), characterized by clinically normal appearing mucosa sited at a distance from co-existing OPMLs, and non-dysplastic OPMLs may also represent an early pre-cancerous state. ODFs, OPMLs without and with dysplasia and OSCCs were investigated by high resolution
DNA content flow cytometry (FCM). ODFs and OPMLs without dysplasia were
DNA aneuploid respectively in 7/82 (8.5%) and 25/109 (23%) cases. "True normal oral mucosa" and human lymphocytes from healthy donors were
DNA diploid in all cases and were used as sex specific
DNA diploid controls. Dysplastic OPMLs and OSCCs were
DNA aneuploid in 12/26 (46%) and 12/13 (92%) cases. The
DNA aneuploid sublines were characterized by the
DNA Index (DI not =1).
Aneuploid sublines in ODFs and in non-dysplastic and dysplastic OPMLs were near-diploid (DI<1.4) respectively in all, 2/3 and 1/3 of the cases.
DNA aneuploid OSCCs, instead, were characterized prevalently by multiple
aneuploid sublines (67%), which were commonly (57%) high-
aneuploid (DI> or =1.4).
DNA near-diploid
aneuploid sublines in ODFs and OPMLs appear as early events of the oral
carcinogenesis in agreement with the concept of field effect. Near-diploid aneuploidization is likely to reflect mechanisms of loss of symmetry in the chromosome mitotic division. High
DNA aneuploid and multiple sublines in OPMLs with dysplasia and OSCCs suggest, instead, mechanisms of "endoreduplication" of diploid and near-diploid
aneuploid cells and chromosomal loss. High resolution
DNA FCM seems to enable the separation of subsequent progression steps of the oral
carcinogenesis.