Interplay of Transforming Growth Factor-Beta 1 and 3 in the Pathogenesis of Oral Submucous Fibrosis and Its Malignant Transformation: An Immunohistochemical Study.

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Introduction Oral submucous fibrosis (OSF) is a chronic and potentially malignant oral condition that poses a significant public health issue due to its insidious nature. Transforming growth factor-beta (TGF-β) is a key player in the pathogenesis of OSF and is responsible for fibrosis. This study aims to investigate the relationship between the expression of TGF-β1 and TGF-β3 in OSF and its malignant transformation by using immunohistochemistry. Materials and method The present study comprised of 120 formalin-fixed paraffin-embedded tissue samples, which included 20 normal oral mucosa (NOM), 80 OSF (20 each of stage 1- 4), and 20 oral squamous cell carcinoma (OSCC) (10 each of OSCC with and without OSF), and were stained for TGF-β1 and TGF-β3 by immunohistochemistry. Data were analyzed using R software version 4.1.2, GraphPad Prism 9.3.1 (GraphPad Software,San Diego, CA, USA) and Excel (Microsoft Corp., Redmond, WA). Results TGF-β1 immunoexpression was negative in NOM with no significant difference among OSF and OSCC (with or without OSF). TGF-β3 was significantly higher in OSCC (with or without OSF) than in OSF, and no significant difference was noted between OSF and NOM and between OSCC and NOM. A significant increase was seen in TGF-β3 compared to TGF-β1 in NOM, OSF (stage 1- 4), and OSCC with and without OSF. Conclusion TGF-β3 has higher immunoexpression levels than TGF-β1 in NOM, OSF, and OSCC. We speculate that quantitative or qualitative TGF- β3 may be inadequate to prevent or attenuate fibrosis in OSF patients. There is also a modicum of probability that TGF-β3 has a preventive rather than causative role in OSF pathogenesis. The role of TGF-β3 in OSF needs further clarification.