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

Sep 22, 2026

Hemidesmosomal subunits are implicated in the progression of oral squamous cell carcinoma (OSCC), yet quantitative expression patterns linked to disease pathogenesis remain insufficiently characterized. This study assessed key, underexplored hemidesmosomal subunits—plectin isoform Ia (PIa), dystonin, and CD151 antigen—across normal tissue and lesions progressing from hyperplasia and dysplasia to OSCC in both human and murine oral cavity.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

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Abstract

Background

Methods

Results

Conclusion

Introduction

Journal of Oral Pathology & Medicine ORIGINAL ARTICLE OPEN ACCESS Hemidesmosomal Proteins in Oral Cancer Progression: An Immunohistochemical Study of Human and Mouse Nikhil Mongia1 | Ali Ibrahim Mohammed1 | Michael McCullough1 | Rita Paolini1 | James A. Rickard2,3 | Massimo Mascolo4 | Silvia Varricchio4 | Lorraine A. O'Reilly5,6 | John Silke5,6 | Nicola Cirillo1 | Antonio Celentano1 1Melbourne Dental School, The University of Melbourne, Carlton, Victoria, Australia | 2Austin Hospital, Heidelberg, Victoria, Australia | 3Dorevitch Pathology, Heidelberg, Victoria, Australia | 4Department of Advanced Biomedical Sciences, Unit of Pathology, University of Naples Federico II, Naples, Italy | 5The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia | 6Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia Correspondence: Antonio Celentano ([antonio.celentano@unimelb.edu.au](antonio.celentano@unimelb.edu.au)) Received: 3 December 2025 | Revised: 17 March 2026 | Accepted: 13 April 2026 Keywords: CD151 antigen | dystonin | hemidesmosomal proteins | oral squamous cell carcinoma | plectin isoform Ia (PIa) ABSTRACT 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 amurine model. | Abbreviations: 4-NQO, 4-Nitroquinoline 1-oxide; CIS, cancer in situ; Col17/BPAG2/BP180/COL17AI, Collagen Type 17 Alpha 1; DAB, 3–3′ diaminobenzidine; Erk1/2, extracellular signal-regulated kinase 1/2; FFPE, formalin-fixed paraffin-embedded; HRP, horseradish peroxidase; ICC, intraclass correlation coefficient; IHC, immunohistochemistry; OPMD, oral potentially malignant disorders; OSCC, oral squamous cell carcinoma; PBS, phosphate buffer saline; PBS, phosphate buffer saline; PIa, plectin isoform 1a; TMA, tissue microarray.
Nikhil Mongia and Ali Ibrahim Mohammed are co-first authors. | | --- | | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs

FAQs

Which hemidesmosomal proteins were evaluated in the study?

The study evaluated plectin isoform Ia (PIa), dystonin, and CD151 antigen, comparing their expression across normal tissue and progressive lesion stages including OSCC.

How was OSCC modeled and how were tissues analyzed?

Immunohistochemistry was performed using custom-built human tissue microarrays and 4-Nitroquinoline 1-oxide (4-NQO)-induced murine OSCC. Quantitative image analysis was conducted with QuPath, including a basement membrane zone-focused approach in human tissues.

What key expression differences were reported between murine and human tissues?

In murine tissues, expression of all three proteins increased across normal, hyperplasia, dysplasia, and OSCC. In humans, the basement membrane zone-focused analysis showed sustained baseline expression and reductions in CD151 antigen and dystonin in OSCC versus control/high-grade dysplasia groups.

Sep 22, 2026

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