Immunohistochemical Localization of Epithelial Mesenchymal Transition Markers in Cyclosporine A Induced Gingival Overgrowth ZC048-ZC052
Dr. Suresh Ranga Rao,
Professor and Head of Department, Department of Periodontics, Faculty of Dental Sciences,Sri Ramachandra University,
No.1 Ramachandra Nagar, Porur, Chennai- 600116, India.
Introduction: Cyclosporine, an immunosuppressive agent used in the management of renal transplant patients is known to produce Drug Induced Gingival Overgrowth (DIGO) as a side effect. Several mechanisms have been elucidated to understand the pathogenesis of DIGO. Recently, epithelial mesenchymal transition has been proposed as a mechanism underlying fibrosis of various organs.
Aim: The aim of the study was to investigate if Epithelial Mesenchymal Transition (EMT) operates in Cyclosporine induced gingival overgrowth.
Materials and Methods: The study involved obtaining gingival tissue samples from healthy individuals (n=17) and subjects who exhibited cyclosporine induced gingival overgrowth (n=18). Presence and distribution of E-Cadherin, S100 A4 and alpha smooth muscle actin (a-SMA) was assessed using immunohistochemistry and cell types involved in their expression were determined. The number of a– SMA positive fibroblasts were counted in the samples.
Results: In control group, there was no loss of E-Cadherin and a pronounced staining was seen in the all layers of the epithelium in all the samples analysed (100%). S100 A4 staining was noted in langerhans cells, fibroblasts, endothelial cells and endothelial lined blood capillaries in Connective Tissue (CT) of all the samples (100%) while a - SMA staining was seen only on the endothelial lined blood capillaries in all the samples (100%). However in DIGO, there was positive staining of E-Cadherin only in the basal and suprabasal layers of the epithelium in all the samples (100%). Moreover there was focal loss of E-Cadherin in the epithelium in eight out of 18 samples (44%). A break in the continuity of the basement membrane was noted in three out of 18 samples (16%) on H & E staining.
Conclusion: Based on the analysis of differential staining of the markers, it can be concluded that EMT could be one of the mechanistic pathways underlying the pathogenesis of DIGO.