Vigabatrin-induced modification of Ki-67 expression in gingival epithelium: immunohistochemical study of a short series

Objective: To study the expression and role in vigabatrin (VGB)-induced gingival enlargement of Ki-67 antigen and p27(KIP1), p21(WAF1), and p53, proteins that activate or inhibit cell-cycle progression. Materials and methods: Six patients treated with VGB for partial epileptic seizures refractory to classic anticonvulsant treatment were studied. Gingival biopsies were taken from four of these patients for immunohistochemical studies; 10 control biopsies from individuals with healthy gingiva and 10 from patients with periodontal disease were also evaluated. Results: Four of the six patients presented some degree of gingival enlargement (mild or moderate). Nuclear expression of Ki-67 was elevated (mean of 894 positive cells/mm(2) in VGB-induced gingival enlargement vs. 391 cells/mm(2) in controls with healthy gingiva and 425 cells/mm(2) in controls with periodontal disease) (p < 0.01, analysis of variance: ANOVA), and nuclear expression of cyclin-dependent kinase (cdk) inhibitors p27(KIP1) and p21(WAF1) was reduced. The patients with gingival enlargement presented inflammatory infiltrate in lamina propria, mainly composed of T lymphocytes (CD3(+)) and plasma cells (CD38(+)), which was even more intense than in the biopsies of patients with periodontal disease. Conclusion: The overexpression of antigen Ki-67 and slight underexpression of cdk-inhibitors p27(KIP1) and p21(WAF1) suggest that VGB induced an increase in cell proliferation and contributed, together with concomitant periodontal disease, to the gingival enlargement.