The Patterns of P53, E-Cadherin, β-Catenin, CXCR4 and Podoplanin Expression in Oral Squamous Cell Carcinoma Suggests a Hybrid Invasion Model: an Immunohistochemical Study on Tissue Microarrays

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Heguedusch, Daniele ; Carvalho, Giovanna Lopes ; Tomo, Saygo ; Aguiar, Emilia Maria Gomes ; Custodio, Marcos ; Siqueira, Juliana Mota ; Mercante, Ana Maria da Cunha ; Cury, Patricia Maluf ; Tajara, Eloiza Helena ; De Cicco, Rafael ; Nunes, Fabio Daumas

• Document type: Journal article
• Source: Head and Neck Pathology; v. 19, n. 1, p. 12-pg., 2025-01-07.

Abstract

PurposeOral squamous cell carcinoma (OSCC) is a significant public health challenge associated with high mortality rates primarily due to its invasive and metastatic behavior. This study aimed to evaluate the expression patterns of five critical biomarkers: beta-catenin, E-cadherin, podoplanin (PDPN), CXCR4, and p53 in OSCC tissues and to investigate their correlations with clinicopathologic features and patient outcomes.MethodsWe conducted an immunohistochemical analysis utilizing tissue microarrays (TMAs) from 95 patients diagnosed with primary OSCC. The expression levels of the five biomarkers were quantified using H-scores. Statistical analyses, including Kruskal-Wallis tests, Dunn's post-hoc tests, and correlation analyses, were performed to explore the associations between biomarker expression, clinicopathologic parameters, and overall patient survival.ResultsThe study found that loss of E-cadherin and beta-catenin expression was significantly associated with increased tumor depth and lymphatic invasion, corroborating their role in the process of epithelial-mesenchymal transition (EMT). High levels of PDPN were noted in both early and late-stage OSCC, indicating its potential involvement in initiating invasive behaviors. Notably, CXCR4 expression exhibited positive correlations with E-cadherin and beta-catenin, suggesting a hybrid invasion phenotype incorporating both EMT and collective invasion strategies. Although Cox regression analysis did not reveal significant associations between biomarker expression and overall survival (OS) or disease-specific survival (DSS), factors such as alcohol consumption, tumor size, lymph node involvement, and advanced clinical stage emerged as significant negative predictors of both OS and DSS.ConclusionThe expression profiles of beta-catenin, E-cadherin, PDPN, CXCR4, and p53 in OSCC tissues provide valuable insights into a hybrid model of invasion that integrates mechanisms of EMT with an important rule in the tumor invasion. This nuanced understanding of OSCC progression highlights the potential of PDPN and CXCR4 as novel therapeutic targets, emphasizing the need for further investigation into their roles in OSCC biology and the development of targeted treatments that could improve patient outcomes and survival rates. (AU)

• FAPESP's process: 10/51168-0 - Environmental, clinical, histopathological and molecular factors associated with development and prognosis of head and neck squamous cell carcinomas
• Grantee: Eloiza Helena Tajara da Silva
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 23/11402-4 - Regulated necrosis induced by photodynamic and sonodynamic therapies in oral epithelial dysplastic cells: in vitro and in vivo study
• Grantee: Saygo Tomo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral