Atypical mitoses in lesions of the oral mucosa: a new interpretation of their impact upon tumorigenesis.
With regard to the classification of precancerous lesions, this is the first approach to compare modes of the cell cycle in benign lesions and neoplasia in oral mucosa. The main objective of this study was to find parameters that indicate possible progress in tumorigenesis. In this respect, histomorphological changes were compared with the DNA content of individually identified nuclei in interphase and division. Thus, hyperplastic tissue was discriminated from neoplastic tissue by investigating pyogenic granulomas (27 cases), epulides (17), simple forms of ulcers (12), low-grade dysplasias (14), high-grade dysplasias (15) and carcinomas (41). After diagnosis, Feulgen DNA was quantified from interphase nuclei and chromosome division figures (CDFs) in 8- and 15-micron sections. Interphase nuclei from cases of hyperplasia were constantly found in the range of mitotic amounts, i.e. 2 c-4 c DNA. A 4 c value was therefore recorded for mitotic figures. Measurements in this type of lesion were carried out with a high degree of accuracy (CV at 0.05). However, cases of neoplasia showed CDFs that were frequently beyond the mitotic range (> 4.8 c) in morphologically identified prophases, metaphases and both hemispheres of telophases. The distribution profile of interphase nuclei was characterised by DNA aneuploidy, with a 5 c exceeding rate (ER) > 5%. This biological variability in the amount of nuclear DNA was reflected by CV > 0.20. The quantitative results corroborated the morphological two-level classification of premalignant lesions caused by endoreplication associated with neoplasia. Thus, regular mitotic replication appeared to be progressively substituted by genome multiplication.
Steinbeck
R G
RG
Department of Tumor Pathology, Karolinska Institute and Hospital, Stockholm, Sweden.
D002454:Cell Differentiation; D004247:DNA / Q000032:analysis; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007150:Immunohistochemistry; D007399:Interphase / Q000502:physiology; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D008940:Mitotic Index; D009061:Mouth Mucosa / Q000737:chemistry / Q000473:pathology*; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D011003:Ploidies; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen; D004247:DNA