A case report of multiple-drug-induced gingival overgrowth with TIMP-3 over-expression

Abstract

A case of multiple-drug-induced gingival overgrowth (GO) in a 46-year-old male is reported. The patient exhibited severe gingival enlargement throughout the entire mandible and maxilla with a history of multiple medications for psychiatric and internal diseases. A gingivectomy specimen was examined pathologically and further analyzed using immunohistochemical and molecular biological methods for the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Histologically, the gingival overgrowth was due to fibrous granulation tissue with hyperplastic collagen bundles and squamous epithelia, and the lesion was pathologically diagnosed as drug-induced gingival hyperplasia. An enhanced transcript level for TIMP-3 but reduced levels for MMPs and cathepsin L were quantitatively determined by RT-PCR. TIMP-3 was strongly immunohistochemically localized in fibroblasts and endothelial cells. DNA invader genotyping revealed that the patient carried one GO-related allele (α2 integrin +807C). These findings showed that, in this GO case, collagen accumulation in the gingival granulation tissue was associated with decreased MMPs and increased TIMP-3 expression, which was suggested to be synergistically induced by simultaneous and multiple medications, including nifedipine and antipsychotic drugs.