title: Oral cancer genesis and progression: DNA near-diploid aneuploidization and endoreduplication by high resolution flow cytometry.
abstract: 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.
authors.affiliation: Department of Diagnostic Oncology, Biophysics and Cytometry Section, National Cancer Research Institute, Genoa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Donadini
authors.forename: Massimo
authors.initials: M
authors.lastname: Maffei
authors.forename: Antonio
authors.initials: A
authors.lastname: Cavallero
authors.forename: Monica
authors.initials: M
authors.lastname: Pentenero
authors.forename: Davide
authors.initials: D
authors.lastname: Malacarne
authors.forename: Emanuela
authors.initials: E
authors.lastname: Di Nallo
authors.forename: Mauro
authors.initials: M
authors.lastname: Truini
authors.forename: Roberto
authors.initials: R
authors.lastname: Navone
authors.forename: Paola
authors.initials: P
authors.lastname: Mereu
authors.forename: Marco
authors.initials: M
authors.lastname: Scala
authors.forename: Alida
authors.initials: A
authors.lastname: Santelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Gandolfo
authors.forename: Walter
authors.initials: W
authors.lastname: Giaretti
mesh_terms: D000328:Adult; D000368:Aged; D000782:Aneuploidy; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007972:Leukoplakia, Oral / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D011230:Precancerous Conditions
chemical_list: D004273:DNA, Neoplasm