AKT3 and α-SMA in oral submucous fibrosis and oral squamous cell carcinoma with concomitant oral submucous fibrosis as potential prognostic indicators.

PURPOSE: Oral squamous cell carcinoma (OSCC) concomitant with oral submucous fibrosis (OSCC-OSMF) is a clinico-pathologically distinct entity. Myofibroblasts (MFs) and its differentiation plays pivotal role in tumour progression via cell cycle alterations, epithelial-mesenchymal transition (EMT), hypoxia, immunomodulatory disorders, oxidative injury and epigenetic modifications. OBJECTIVE: The present study evaluated immunohistochemical expression of AKT3 and alpha-smooth muscle actin amongst, OSMF and OSCC-OSMF and correlated with related clinicopathological parameters. MATERIALS AND METHODS: 70 formalin-fixed paraffin-embedded tissue samples of histopathologically confirmed cases, including 10 NOM, 30 OSMF, and 30 OSCC-OSMF, were immunohistochemically stained with AKT3 and (α-SMA) antibodies to quantify MFs and myofibroblastic cancer associated myofibroblasts (myCAFs). RESULTS: The percentage of α-SMA and AKT3 positive cells was statistically significant within the OSMF and OSCC-OSMF study groups (P < 0.0001). A progressive increase in cytoplasmic expression of α-SMA and AKT3 was observed from NOM to OSMF and OSCC-OSMF. A statistically significant correlation was found between the stages of OSMF and the clinical TNM stages of OSCC-OSMF. CONCLUSION: Increased stromal expression of α-SMA and AKT3 is associated with disease progression in OSMF and OSCC-OSMF. This is the first study to investigate AKT-3 expression in OSMF and OSCC arising in OSMF, and these markers may serve as potential indicators of stromal activation and tumour progression, thereby warranting further longitudinal and functional investigations.