OBJECTIVE: Oral squamous cell carcinoma (OSCC) originates from the mucosal lining of the oral cavity. Almost half of newly diagnosed cases are classified as advanced stage IV disease, which makes resection difficult. In this study, we investigated the pathological features and mutation profiles of tumor margins in OSCC. METHODS: We performed hierarchical clustering of principal components to identify distinct patterns of tumor growth and their association with patient prognosis. We also used next-generation sequencing to analyze somatic mutations in tumor and marginal tissue samples. RESULTS: Our analyses uncovered that the grade of worst pattern of invasion (WPOI) is strongly associated with depth of invasion and patient survival in multivariable analysis. Mutations were primarily detected in the DNA isolated from tumors, but several mutations were also identified in marginal tissue. In total, we uncovered 29 mutated genes, mainly tumor suppressor genes involved in DNA repair including BRCA genes; however none of these mutations significantly correlated with a higher chance of relapse in our medium-size cohort. Some resection margins that appeared histologically normal harbored tumorigenic mutations in TP53 and CDKN2A genes. CONCLUSION: Even histologically normal margins may contain molecular alterations that are not detectable by conventional histopathological methods, but NCCN classification system still outperforms other methods in the prediction of the probability of disease relapse.

Department of Craniofacial Surgery Faculty of Medicine Ostrava University Ostrava Ostrava Czechia

Department of Environmental Engineering VSB Technical University of Ostrava Ostrava Czechia

Department of Experimental Biology Faculty of Science Masaryk University Brno Czechia

Department of Hematooncology University Hospital Ostrava Ostrava Czechia

Department of Histology and Embryology Faculty of Medicine Masaryk University Brno Czechia

Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD United States

Department of Oncology University Hospital Ostrava Ostrava Czechia

Department of Oral and Maxillofacial Surgery University Hospital Ostrava Ostrava Czechia

Department of Otorhinolaryngology Head and Neck Surgery Marlene and Stewart Greenebaum Comprehensive Cancer Center University of Maryland Medical Center Baltimore MD United States

Department of Otorhinolaryngology University Hospital Ostrava Ostrava Czechia

Department of Pathological Morphology and Parasitology University of Veterinary Sciences Brno Brno Czechia

Institute for Genome Sciences University of Maryland School of Medicine Baltimore MD United States

Institute of Animal Physiology and Genetics Czech Academy of Sciences Brno Czechia

Institute of Clinical and Molecular Pathology Faculty of Medicine University of Ostrava Ostrava Czechia

Institute of Clinical and Molecular Pathology University Hospital Ostrava Ostrava Czechia

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BRCA1 and BRCA2 as prognostic markers in oral squamous cell carcinoma: a minireview