Epithelial Mesenchymal Transition in Gingival Overgrowth

BACKGROUND: Epithelial Mesenchymal Transition (EMT) is a complex process in which epithelial cells gain mesenchymal characteristics in fibrosis and cancer. AIM: To study EMT as a potential mechanism in gingival overgrowth. METHODS: Gingival overgrowth (GO) samples were from patients receiving phenytoin (PHE; n=8), nifedipine (NIF; n=8), or cyclosporin-A (CsA; n=7), or diagnosed with gingival fibromatosis (GF; n=7). Control tissues were from healthy donors (n=12). Tissue sections were analyzed by peroxidase immunohistochemistry using E-cadherin (specific marker of epithelium) or Fibroblast Specific Protein-1 (Fsp-1) antibodies. Staining was evaluated in oral sulcular epithelium, oral epithelium and sub-epithelial connective tissue. Epithelial layers were further analyzed as Stratum basale, mid-epithelium, and Stratum corneum; evaluation was made using a semiquantitative grading ranging from 0 (no staining) to 4 (dense staining) and data was presented as arbitrary units (AU). Fibroblasts were counted in sub-sulcular and sub-oral connective tissue and Fsp-1+ cells were normalized to the total number of fibroblasts. ANOVA with Tukey correction was used to evaluate the data. RESULTS: E-cadherin levels in GO samples were significantly lower compared to control tissues (Stratum basale: 0.19±0.08AU vs. 0.84±0.32AU; mid-epithelium: 2.03±0.18AU vs. 3.27±0.24AU; Stratum corneum: 0.19±0.09AU vs. 2.39±0.26AU; respectively; p<0.01) while there was no detectable expression in fibroblasts. Different types of GO demonstrated similarly reduced expression of E-cadherin. Epithelial Fsp-1 showed a significant increase in Stratum corneum of oral epithelium of GO samples compared to control tissues (p<0.05) while Stratum basale of sulcular epithelium in CsA group showed significantly higher epithelial Fsp-1 content compared to GF, PHE, and control samples (p<0.05). GF samples had significantly lower (p<0.001) percentage of Fsp-1+fibroblasts (6.69±4.76%) compared to control (33.13±4.57%), PHE (48.48±5.83%), NIF (55.21±7.05%), and CsA (54.12±7.83%) in connective tissue beneath the subsulcular epithelium. CONCLUSIONS: EMT may be an underlying mechanism in the pathogenesis of gingival overgrowth. Supported by USPHS Grants DE11004 and RR00533.