Study on Subcellular Expression Patterns of p62/SQSTM1 in Oral Squamous Cell Carcinomas: An Immunohistochemical Analysis

Abstract

ABSTRACT Background p62/SQSTM1 is a multifunctional 62 kDa protein that shuttles between the nucleus and cytoplasm to maintain protein homeostasis through the autophagy machinery. Dysregulated p62 acts as an oncogenic signalling hub, activating pathways such as NF-κB, Nrf2, and mTORC1 that promote tumour cell proliferation and resistance to cell death in malignancy.This study aimed to assess the subcellular expression patterns of p62 in OSCCs by an immunohistochemical approach. Study design This is an observational in vitro cross sectional study done using a total 45 oral tissue specimens (N=45). Method The 45 tissue samples consist of 30 OSCC specimens, and 15 Normal oral mucosal specimens. These samples were sectioned and tissue were stained with H& E stain for histopathological confirmation and IHC staining with p62 marker for assessment.Microscopic evaluation of p62 immunohistochemical stained tissue sections was done by two blinded observers for subcellular p62 staining and a semiquantitative score were calculated. The results were statistically analysed with a significance of p-value at <0.05 Results Subcellular expression of p62 was significantly upregulated in all grades of OSCC compared to Normal oral mucosal epithelum, where minimal physiological expression was observed. In well-differentiated OSCC, p62 expression was significantly higher in the nucleus compared to controls. Progressive shift towards the cytoplasmic localisation was observed in moderate OSCCs. Poorly differentiated OSCCs exhibited the highest cytoplasmic Q values (p < 0.001) and significantly lower nuclear levels (p = 0.012). Conclusion High nuclear p62 accumulation observed in early stage OSCCs, and medium to high cytoplasmic p62 expression in moderately to poorly differentiated OSCCs. Subcellular p62 expression shifts from the nucleus to the cytoplasm during high-grade malignant transformation, serving as a marker for impaired autophagy and abnormal cell proliferation. Key words p62, Autophagy, Cell proliferation,Oral squamous cell carcinoma, Nuclear expression, Cytoplasmic expression.