Hemidesmosomal Proteins in Oral Cancer Progression: An Immunohistochemical Study of Human and Mouse

BACKGROUND: Hemidesmosomal subunits have gained attention for their potential role in the progression of oral squamous cell carcinoma (OSCC). However, formal analysis of quantitative expression patterns correlating with OSCC disease pathogenesis remains limited. This study evaluated the expression of key yet overlooked hemidesmosomal subunits, plectin isoform Ia (PIa), dystonin, and CD151 antigen, from normal tissue as well as tissue from hyperplasia, dysplasia, and OSCC in the human and murine oral cavity. METHODS: Immunohistochemistry was performed on custom-built human tissue microarrays and 4-Nitroquinoline 1-oxide (4-NQO)-induced murine OSCC covering the spectrum of histological changes from normal to cancer. Quantitative image analysis of subunit expression was conducted using QuPath, with distinct analytical approaches applied to human tissues, including a refined method focusing on the basement membrane zone (BMZ) and adjacent basal epithelial layers, key sites of hemidesmosomal protein localization. RESULTS: A significant increase in expression of all three proteins was observed comparing normal tissue with hyperplasia, dysplasia, and OSCC in murine tissues, but not in humans. The expression of hemidesmosomal proteins increased across this spectrum, suggesting their potential as progression biomarkers in mice. A focused analysis of the basement membrane zone and adjacent basal epithelial layers in human tissues revealed a sustained baseline expression and a significant reduction in CD151 antigen in OSCC compared with control and high-grade dysplasia groups, as well as a significant reduction in dystonin expression in OSCC compared to high-grade dysplasia. CONCLUSION: Our findings highlight the importance of biologically targeted region-of-interest selection when assessing hemidesmosomal protein expression in OSCC while demonstrating that BMZ-focused digital analysis provides a more informative approach for exploratory evaluation of heterogeneous human tissues alongside progression-associated patterns observed in a murine model.