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Objective <p>Laryngeal squamous cell carcinoma (LSCC) is a tumor characterized by high biological heterogeneity. According to our literature review, this study is the first to analyze the expression profiles of EGFR, p16, E-cadherin, and EBER in combination with epithelial–mesenchymal transition (EMT) and tumor budding (TB), which represent the most critical dynamics of the invasive tumor front, and to demonstrate the quantitative hierarchy among these parameters. The aim of this study was to determine the independent predictive value of these biomarkers in identifying the aggressive phenotype.</p> Materials and methods <p>A total of 61 LSCC cases were included in this retrospective cohort study. Tumor budding (according to ITBCC 2016 criteria), EMT, perineural invasion (PNI), and tumor-infiltrating lymphocytes (TILs) were evaluated histopathologically. EGFR, p16, and E-cadherin expression were assessed by immunohistochemistry, while EBER status was evaluated using in situ hybridization (SISH). The data were modeled using binary logistic regression analysis.</p> Results <p>Tumor budding was detected in 54.1% of the cases, while EMT was observed in 37.7%. According to multivariate analysis, EGFR positivity increased the risk of an aggressive phenotype by 50.058-fold (<i>p</i>=0.018), and p16 positivity increased the risk by 17.818-fold (<i>p</i>=0.004), identifying them as the strongest independent risk factors.</p> <p>Preservation of E-cadherin reduced the risk by 95% (OR: 0.049, <i>p</i>=0.016). No independent association was found between EBER expression or TIL presence and the aggressive phenotype (<i>p</i>&gt;0.05).</p> Conclusion <p>This study demonstrates that a molecular signature characterized by EGFR and p16 positivity together with loss of E-cadherin identifies the most aggressive subgroup of LSCC patients, characterized by high-grade tumor budding and EMT. As the first study integrating this four-marker molecular panel with invasive tumor front parameters, our findings provide a novel prognostic perspective in laryngeal carcinogenesis.</p>

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The relationship of EBER, EGFR, p16, and E-cadherin expressions with epithelial-mesenchymal transition and tumor budding in laryngeal squamous cell carcinoma

  • 期刊论文

  • 发表日期：

    2026年7月23日

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  • Özgecan Gündoğar,
  • Sibel Bektaş,
  • Pelin Akbaş,
  • Fatih Tetik

摘要

Objective

Laryngeal squamous cell carcinoma (LSCC) is a tumor characterized by high biological heterogeneity. According to our literature review, this study is the first to analyze the expression profiles of EGFR, p16, E-cadherin, and EBER in combination with epithelial–mesenchymal transition (EMT) and tumor budding (TB), which represent the most critical dynamics of the invasive tumor front, and to demonstrate the quantitative hierarchy among these parameters. The aim of this study was to determine the independent predictive value of these biomarkers in identifying the aggressive phenotype.

Materials and methods

A total of 61 LSCC cases were included in this retrospective cohort study. Tumor budding (according to ITBCC 2016 criteria), EMT, perineural invasion (PNI), and tumor-infiltrating lymphocytes (TILs) were evaluated histopathologically. EGFR, p16, and E-cadherin expression were assessed by immunohistochemistry, while EBER status was evaluated using in situ hybridization (SISH). The data were modeled using binary logistic regression analysis.

Results

Tumor budding was detected in 54.1% of the cases, while EMT was observed in 37.7%. According to multivariate analysis, EGFR positivity increased the risk of an aggressive phenotype by 50.058-fold (p=0.018), and p16 positivity increased the risk by 17.818-fold (p=0.004), identifying them as the strongest independent risk factors.

Preservation of E-cadherin reduced the risk by 95% (OR: 0.049, p=0.016). No independent association was found between EBER expression or TIL presence and the aggressive phenotype (p>0.05).

Conclusion

This study demonstrates that a molecular signature characterized by EGFR and p16 positivity together with loss of E-cadherin identifies the most aggressive subgroup of LSCC patients, characterized by high-grade tumor budding and EMT. As the first study integrating this four-marker molecular panel with invasive tumor front parameters, our findings provide a novel prognostic perspective in laryngeal carcinogenesis.