Cell cycle regulating mechanisms in oral lichen planus: molecular bases in epithelium predisposed to malignant transformation.
OBJECTIVE: Expression of p53, p21, ki-67, Bcl-2 and caspase-3 proteins in oral lichen planus (OLP) was studied to investigate cell cycle regulation mechanisms in this disease. MATERIAL AND METHODS: Oral biopsies were obtained from 51 patients with OLP and 26 controls for immunohistochemical analysis (peroxidase antiperoxidase) to quantify expression of the proteins under study (-: 0%, +: <10%, ++: 10-25%, +++: 26-50%, ++++: >50% positive cells). RESULTS: Basal expression of caspase-3 was negative in 22 cases (46.8%) and positive in <10% of basal cells in 22 cases (46.8%); caspase-3 expression in inflammatory infiltrate was negative in 22 cases (46.8%) and positive in <10% of lymphocytes in 20 cases (42.5%). Basal expression of Bcl-2 was negative in 35 cases (74.5%); Bcl-2 was expressed in inflammatory infiltrate in 34 cases (72.3%) and was positive in <25% of lymphocytes in 14 of these (29.7%). Basal expression of p53 and p21 was positive in 32 (67.9%) and 23 (48.8%) cases, respectively. Basal expression of ki-67 was positive in 45 cases (95.7%), of which 20 (42.5%) showed positivity in >25% of cells; ki-67 was expressed in inflammatory infiltrate in 23 cases (48.9%). Significant associations were found between basal expressions of p53 and ki-67 (p<0.001) and between Bcl-2 expression in infiltrate and basal expression of ki-67 (p<0.001). No association was observed between basal expressions of p53 and caspase-3 (p=0.08). Bcl-2 expression in infiltrate and basal expression of ki-67 were independently associated with presence of OLP. CONCLUSIONS: Epithelial cells in OLP do not preferentially develop apoptosis but rather cycle arrest or an increased proliferation rate, which may create a suitable substrate for malignant transformation.