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To clarify changes in cell proliferation and the mechanism behind phenytoin (PHT)-induced gingival overgrowth, representative medication-induced gingival overgrowth, we immunohistochemically studied gingival tissues from patients with PHT gingival overgrowth (PHT-GO), comparing them to those with proliferative gingivitis secondary to the presence of dental plaque (ND) and clinically healthy gingiva (controls) . Five patients from each of the above types ofgingiva were selected randomly and biopsies obtained during periodontal surgery or tooth extraction, processed routinely in paraffin wax, and serially sectioned. These specimens were immunostained using mouse antiproliferating cell nuclear antigen (PCNA) monoclonal antibody. Fibroblasts and epithelial cells in each group contained immunoreactive products. Many PCNA-positive cells were recognized in the PHT-GO group, but few positive cells appeared in elongated rete pegs. The number of total fibroblasts per unit area of connective tissue adjacent to the oral epithelium was significantly greater in the PHT-GO group than in other groups (p<0.01) , with no statistical significance seen between ND and controls. The density of PCNA-positive fibroblasts was highest in PHT-GO and declined in ND and controls. Statistically significant differences were found between PIIT GO and ND groups (p<0.05), PHT-GO and controls (p<0.01), and ND and controls (p< 0.01). Comparisons of frequency in PCNA-positive fibroblasts between highly and poorly inflammatory cell-infiltrated areas in connective tissues showed no significant difference in PHT-GO and ND. These findings suggest the possibility of enhancement in proliferation of fibroblasts in PHT-GO. The number of infiltrated inflammatory cells was not related, however, to that of proliferating fibroblasts. In summary, the mechanism behind the appearance of PHT-induced gingival overgrowth appears to be the increase in PCNA-positive fibroblasts resulting in an increase in gingival fibroblasts. J. Jpn. Soc. Periodontol., 42: 314 322, 2000.

An Immunohistochemical Study Using Antiproliferating Cell Nuclear Antigen (PCNA) Antibody in Human Gingival Tissue Overgrowth Induced by Phenytoin.