title: Immunohistochemical Localization of Epithelial Mesenchymal Transition Markers in Cyclosporine A Induced Gingival Overgrowth.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The aim of the study was to investigate if Epithelial Mesenchymal Transition (EMT) operates in Cyclosporine induced gingival overgrowth.
  
  
  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 (α-SMA) was assessed using immunohistochemistry and cell types involved in their expression were determined. The number of α- 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 α - 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Post Graduate Student, Department of Periodontics, Faculty of Dental Sciences, Sri Ramachandra University , Porur, Chennai, India .
authors.forename: Hitesh
authors.initials: H
authors.lastname: Arora
authors.affiliation: Associate Professor, Department of Periodontics, Faculty of Dental Sciences, Sri Ramachandra University , Porur, Chennai, India .
authors.forename: Balaji Thodur
authors.initials: BT
authors.lastname: Madapusi
authors.affiliation: Reader, Department of Periodontics, Faculty of Dental Sciences, Sri Ramachandra University , Porur, Chennai, India .
authors.forename: Anjana
authors.initials: A
authors.lastname: Ramamurti
authors.affiliation: Professor and Head of Department, Department of Oral Pathology, Faculty of Dental Sciences, Sri Ramachandra University , Porur, Chennai, India .
authors.forename: Malathi
authors.initials: M
authors.lastname: Narasimhan
authors.affiliation: Professor, Department of Nephrology, Sri Ramachandra Medical College , Sri Ramachandra University , Porur, Chennai, India.
authors.forename: Soundararajan
authors.initials: S
authors.lastname: Periasamy
authors.affiliation: Professor and Head of Department, Department of Periodontics, Faculty of Dental Sciences, Sri Ramachandra University , Porur, Chennai, India .
authors.forename: Suresh Ranga
authors.initials: SR
authors.lastname: Rao
keywords: Drug induced gingival overgrowth; Gingiva; Myofibroblasts