4.1 Article

Cortactin expression in a Norwegian cohort of human papilloma virus negative oral squamous cell carcinomas of the mobile tongue

Journal

EUROPEAN JOURNAL OF ORAL SCIENCES
Volume 131, Issue 2, Pages -

Publisher

WILEY
DOI: 10.1111/eos.12925

Keywords

invasion; organotypic culture; tumor budding

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Oral squamous cell carcinoma of the tongue (OTSCC) is a common and unfavorable malignancy. Overexpression of cortactin is associated with invasion and metastasis of tumor cells. This study investigates the expression pattern and prognostic significance of cortactin in HPV-negative OTSCC, finding that high overall cortactin expression is associated with larger tumor size, distant metastasis, and reduced 5-year survival. Silencing cortactin suppresses the proliferative and invasive abilities of OTSCC cells.
Oral squamous cell carcinoma of the tongue (OTSCC) is the most common malignancy among oral squamous cell carcinomas and is frequently associated with an unfavorable prognosis. Local spread and distant metastasis are important causes of poor prognosis in OTSCC. Cortactin amplification and overexpression, a common molecular alteration in oral squamous cell carcinomas, have been linked to invasion and metastasis of tumor cells. However, the intra-tumor expression pattern and prognostic significance of cortactin in human papillomavirus (HPV) negative OTSCC is not fully investigated. Immunohistochemical analysis using tissue microarray consisting of formalin-fixed and paraffin-embedded HPV negative OTSCC (n = 123) specimens showed overexpression of cortactin at tissue cores from invading fronts as compared to the corresponding center cores. High overall cortactin expression was found to be associated with advanced (larger) tumor size and the occurrence of distance metastasis. Kaplan-Meier survival analysis showed that patients with high overall cortactin expression were associated with reduced 5-year survival. Multivariate Cox regression analysis identified high cortactin expression to be an independent prognostic factor in OTSCC. Additionally, siRNA-mediated silencing of cortactin was found to suppress the proliferative and invasive abilities of OTSCC cells in an organotypic co-culture model. Overexpression of cortactin is a promising prognostic marker in HPV-negative OTSCC.

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