Evaluation of immunohistochemical expression of epithelial–mesenchymal transition markers E-cadherin, Twist and Snail in oral submucous fibrosis and their possible association with malignant transformation

Abstract

Background: Oral submucous fibrosis (OSMF) is a chronic, potentially malignant condition of the oral mucosa, predominantly seen in people of Asian descent. The reported malignant transformation rate of OSMF is 7%–13%. In the context of the understanding progression of OSMF, the study of prime molecular expressions is essential. Various markers have received more attention, one of them is E-cadherin. Various factors which promote epithelial–mesenchymal transition (EMT) and inhibit E-Cadherin include Snail1, Snail2, Twist and EF1/ZEB1. The intended study was undertaken to evaluate the possible role of E-cadherin and its regulatory markers Twist1 and Snail1 in OSMF. Aims and Objectives: To evaluate the expression of E-cadherin, Twist1 and Snail1 in OSMF To evaluate their possible association with malignant transformation of OSMF. Materials and Methods: Histologically proven 20 cases of each OSMF with and without dysplasia were taken as the study group, 20 normal mucosa as control group and were subjected for immunohistochemical (IHC) expression with E-cadherin, Twist1 and snail1. Results: Immunohistochemical expression of all the three markers showed statistically significant expression of all the three markers. Intensity and percentage of staining between the groups were statistically significant for E-cadherin between normal oral mucosa (NOM) and OSMF with dysplasia (OSMFD), no significance was found between NOM and OSMF, whereas Snail1 and Twsit1 were statistically significant between NOM and OSMF and also between NOM and OSMFD. However, no significance was found for all the three markers when compared between the groups OSMF and OSMFD. Conclusion: The increased expression of Snail1 and Twist1 with concomitant loss of E -cadherin in OSMF suggests the role of the EMT.

Enhanced ZEB 1 stromal expression is a marker for epithelial mesenchymal transition in oral submucous fibrosis

“…The most frequent mechanism by which ZEB 1induces EMT related fibrosis is by the activation of TGF-beta pathway. 29 …”

“…ZEB1 expression in the stroma is similar to that found in immune cells and/or a subpopulation of fibroblasts. 29 The presence of ZEB1 in these stromal cells could indicate that it has an impact on the tumor microenvironment. It helps to create the tumor microenvironment by controlling the amounts of inflammatory cytokines like IL-6/8.…”

“…It helps to create the tumor microenvironment by controlling the amounts of inflammatory cytokines like IL-6/8. 29 Extracellular signals generated from the tumor microenvironment abnormally activate the EMT program in cancer cells. The EMT-promoting tumor microenvironment is made up of abnormally increased growth factors, inflammatory cytokines, and some intra-tumoral physical stressors like hypoxia.…”

Integrated Proteomics Based on 2D Gel Electrophoresis and Mass Spectrometry with Validations: Identification of a Biomarker Compendium for Oral Submucous Fibrosis—An Indian Study

“…In 10 high power fields (40X), several positive cells were counted in the epithelium and connective tissue (connective tissue cells like fibroblasts and inflammatory cells), and the % positivity was computed. Counting was done on a computer display using the software ProgRes CapturePro v2.8.8 [19][20][21]. Briefly, CA 1, HSP 70 and 14-3-3ε expression was assessed semi-quantitatively by evaluating the percentage of epithelial and CT cells, 20% or more, expressing the respective proteins considered positive.…”

Is Epithelial-Mesenchymal Transition a New Roadway in the Pathogenesis of Oral Submucous Fibrosis: A Comprehensive Review

“…E‑cadherin, Twist 1, and Snail 1 have been evaluated immunohistochemically in OSMF tissues, and their association with malignant transformation has been demonstrated, suggesting their role in EMT [ 47 ]. A previous study demonstrated an increase in the expression of Snail 1 and Twist with the concomitant loss of E-cadherin [ 48 ]. In addition to the direct effects of transcription factors on gene expression, there also occur some changes at the RNA level to regulate EMT progression such as alternative splicing of nascent RNAs into mRNAs that generate proteins with structural and functional differences in EMT.…”