Mutational Profiles of Cutaneous Squamous Cell Carcinomas with Different Patterns of Clinical Aggression from Head and Neck Regions.

Simple Summary: Cutaneous squamous cell carcinoma (cSCC) ranks among the malignancies with the most pronounced mutation burdens. Understanding its genetic aspects is crucial for improving patient care. This retrospective case-control study compares the molecular profiles of cSCCs in the head and neck regions prone to local recurrence against those without relapse, aiming to identify predictive markers for prognosis and therapy. Using a next-generation sequencing (NGS) array, histological samples from cSCC patients were analyzed, highlighting the most frequently mutated genes in cSCC. Controls displayed a higher mutation count, thus potentially enhancing tumor antigen presentation for the immune system. This immune response might prevent future recurrences, emphasizing the immune system's role in cSCC. The study underscores the importance of novel therapies that leverage the immune system. Cutaneous squamous cell carcinoma is a prevalent malignancy with a rising incidence and a notably high mutational load. Exploring the genetic nuances of cSCC and investigating molecular approaches stands as a potential avenue for improving outcomes in high-risk patients. This retrospective case-control study involved two cohorts, one of 14 patients (the "discovery cohort") and the other of 12 patients (the "validation cohort"), with cSCC located in the head/neck anatomical region and diagnosed at the pT2 stage. Overall, cases developed early local relapses of the disease, whereas controls never relapsed during the entire follow-up period. A next-generation sequencing (NGS) approach conducted on histological samples revealed that TP53 and CDKN2A were the most frequently mutated genes in our series. No specific mutations were identified as potential prognostic or therapeutic targets. Controls exhibited a tendency toward a higher mutational rate compared to cases. It is possible that an increased number of mutations could prompt the cSCC to expose more antigens, becoming more immunogenic and facilitating recognition by the immune system. This could enhance and sustain the immunological response, potentially preventing future recurrences. [ABSTRACT FROM AUTHOR]