Immunohistochemical expression of P16 and β-catenin in oral submucous fibrosis and oral squamous cell carcinoma with or without coexistence of oral submucous fibrosis

Abstract

Background: Oral submucous fibrosis (OSF) is a potentially malignant disorder with 0.4%–10% incidence in India and malignant transformation rate of 3%–19%. Oral squamous cell carcinoma (OSCC) coexistent with OSF exhibits distinct clinicopathological features. Hence, knowledge of the possible mechanism responsible for the epithelial–mesenchymal transition (EMT) of OSF gains importance. The study aims to assess the pattern of p16 and β-catenin expression in normal mucosa (NM), OSF, and OSCC with and without OSF, to correlate with clinicopathological parameters, and to establish association between p16 and β-catenin as markers of EMT. Materials and Methods: Seventy cases, 10 NM, 30 OSF, and 30 OSCC with and without OSF, were subjected to immunohistochemical staining with p16 and β-catenin. Parameters such as percentage positivity and pattern of expression were tabulated and statistically compared using Chi-square test. The combined predictive value of the biomarkers was gauged using discriminant functional analysis. Results: A significant increase in p16% positivity and altered pattern of p16 expression from nuclear to cytoplasmic among the groups (P < 0.001) and a reduced % positivity of β-catenin from NM to OSF and OSCC with and without OSF (P < 0.001). Localization of β-catenin expression shifted from membrane to cytoplasm among groups, which was significantly different in OSCC with and without OSF. The predictive significance of β-catenin and p16 for OSCC with and without OSF was 76.7%. Conclusion: The overexpression of inactivated p16 and synchronous loss of β-catenin expression can be used as an indicator of the early changes during EMT in OSF.