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Enhancing oral squamous cell carcinoma prediction: the prognostic power of the worst pattern of invasion and the limited impact of molecular resection margins

P. Hurník, J. Režnarová, Z. Chyra, O. Motyka, BM. Putnová, Z. Čermáková, T. Blažek, M. Fománek, D. Gaykalova, M. Buchtová, T. Ševčíková, J. Štembírek

. 2023 ; 13 (-) : 1287650. [pub] 20231222

Status not-indexed Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24006141

Grant support
R01 DE027809 NIDCR NIH HHS - United States

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.

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$a OBJECTIVE: Oral squamous cell carcinoma (OSCC) originates from the mucosal lining of the oral cavity. Almost half of newly diagnosed cases are classified as advanced stage IV disease, which makes resection difficult. In this study, we investigated the pathological features and mutation profiles of tumor margins in OSCC. METHODS: We performed hierarchical clustering of principal components to identify distinct patterns of tumor growth and their association with patient prognosis. We also used next-generation sequencing to analyze somatic mutations in tumor and marginal tissue samples. RESULTS: Our analyses uncovered that the grade of worst pattern of invasion (WPOI) is strongly associated with depth of invasion and patient survival in multivariable analysis. Mutations were primarily detected in the DNA isolated from tumors, but several mutations were also identified in marginal tissue. In total, we uncovered 29 mutated genes, mainly tumor suppressor genes involved in DNA repair including BRCA genes; however none of these mutations significantly correlated with a higher chance of relapse in our medium-size cohort. Some resection margins that appeared histologically normal harbored tumorigenic mutations in TP53 and CDKN2A genes. CONCLUSION: Even histologically normal margins may contain molecular alterations that are not detectable by conventional histopathological methods, but NCCN classification system still outperforms other methods in the prediction of the probability of disease relapse.
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$a Režnarová, Jana $u Department of Oral and Maxillofacial Surgery, University Hospital Ostrava, Ostrava, Czechia $u Department of Craniofacial Surgery, Faculty of Medicine, Ostrava University, Ostrava, Ostrava, Czechia
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$a Chyra, Zuzana $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czechia
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$a Motyka, Oldřich $u Department of Environmental Engineering, VSB-Technical University of Ostrava, Ostrava, Czechia
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$a Putnová, Barbora Moldovan $u Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czechia $u Department of Pathological Morphology and Parasitology, University of Veterinary Sciences Brno, Brno, Czechia
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$a Čermáková, Zuzana $u Department of Oncology, University Hospital Ostrava, Ostrava, Czechia
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$a Fománek, Martin $u Department of Otorhinolaryngology, University Hospital Ostrava, Ostrava, Czechia
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$a Gaykalova, Daria $u Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States $u Department of Otorhinolaryngology-Head and Neck Surgery, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, MD, United States $u Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States
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$a Buchtová, Marcela $u Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czechia $u Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czechia
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