Apoptosis, mitosis, PCNA and bcl-2 in normal, leukoplakic and malignant epithelia of the human oral cavity: prospective, in vivo study.

Disordered balance between proliferation and apoptosis may contribute to carcinogenesis. Thirty-two oral biopsies were collected prospectively: 10 normal (N), 10 leukoplakia (dysplasia, D = 5; hyperplasia, H = 5) and 12 squamous cell carcinoma (C: 11). Distant normal tissue was also collected (HN, DN, CN). Based on counts of 1000 cells/slide, mitotic (MI), apoptotic (AI) and proliferating cell nuclear antigen (PCNA: PI) indices were calculated and bcl-2 expression recorded. AI correlated with MI (P < 0.001), but not PI or bcl-2 expression. PCNA was higher in H and HN than other groups (P < 0.0001). bcl-2 was reduced in C and CN (P < 0.001). Peak mitosis shifted basally in dysplasia, whilst peak apoptosis remained unaltered. These data confirm topographical alterations in proliferation relative to apoptosis in dysplasia of the oral cavity. Reduced bcl-2 in carcinoma and related 'normal' epithelium was unexpected, and may contribute to the high incidence of metachronous carcinomas in these patients.