BRCA1 and BRCA2 as Prognostic Markers in Oral Squamous Cell Carcinoma: A minireview

Dominika Gedeonová ^1,2 Claretta Bianchi ^1,3 Jan Štembírek ^1,2,4 Matouš Hrdinka ^1,3 Zuzana Chyra ^5,6 Marcela Buchtova ^4,7 Pavel Hurník ^8,9 Tomáš Blažek ¹⁰ Jana Režnarová ^1,3*

• ¹ Department of Oral and Maxillofacial Surgery, University Hospital Ostrava, Ostrava, Czechia
• ² Department of Craniofacial Surgery, Faculty of Medicine, University of Ostrava, Ostrava, Czechia
• ³ Health research centre, Faculty of Medicine, University of Ostrava, Ostrava, Czechia
• ⁴ Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, South Bohemia, Czechia
• ⁵ Department of Haematooncology, University Hospital Ostrava, Ostrava, Czechia
• ⁶ Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czechia
• ⁷ Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, South Moravia, Czechia
• ⁸ Institute of Molecular and Clinical Pathology and Medical Genetics, Faculty of Medicine, University of Ostrava, Ostrava, Czechia
• ⁹ Institute of Molecular and Clinical Pathology and Medical Genetics, University Hospital Ostrava, Ostrava, Czechia
• ¹⁰ Clinic of Oncology, University Hospital Ostrava, Ostrava, Czechia

Oral squamous cell carcinoma, a subtype of Head and Neck Squamous Cell Carcinoma, typically originates in the epithelial tissue of the gingiva, tongue, buccal mucosa, palate, and oral floor. While OSCC ranks as the sixteenth most common cancer globally, it is the second most widespread in certain high-risk regions (e.g., South Asia), particularly due to the consumption of carcinogen-containing products. In contrast, the increasing incidence of oropharyngeal squamous cell carcinomas in Western countries, including the USA, has been linked to an increase in oropharyngeal human papillomavirus infection. OSCC arises from multifactorial interactions between genetic mutations, environmental exposures, and immune dysregulation, making personalized treatment approaches particularly challenging (Fig1A-D).The progression to invasive OSCC involves a series of cellular changes, beginning with epithelial hyperplasia, progressing through various grades of dysplasia, and culminating in invasive carcinoma. These changes are driven by genomic alterations, which disrupt the balance between oncogenic and suppressor signalling pathways. Oncogenic pathways, including EGFR, PI3K/AKT/mTOR, JAK/STAT, MET, Wnt/β-catenin, and RAS/RAF/MAPK, are often abnormally activated in OSCC, tumor suppressor pathways like TP53/RB, p16/Cyclin D1/Rb, and NOTCH are frequently inactivated.Among these genomic alterations, BRCA1 and BRCA2—genes traditionally associated with breast and ovarian cancers—are emerging as key players in OSCC due to their roles in maintaining genomic stability and regulating DNA damage repair. This review explores the potential of BRCA1/2 as prognostic markers in OSCC by elucidating their involvement in molecular pathways and their diagnostic or therapeutic implications. We aim to provide insights into their significance in OSCC management and patient outcomes.