Association of BRAF Mutation Status with Histopathological Characteristics and Survival Outcomes in Stage II-III...

In patients with advanced or metastatic melanoma, BRAF mutation assessment is routinely performed to identify patients who may benefit from BRAF-targeted therapy. This study aimed to assess the role of BRAF mutation status in relation to histopathological characteristics and survival of patients with stage II and III malignant melanoma. A prospective cohort of 108 patients with pT3 malignant melanoma who were treated in a comprehensive cancer center were included in the analysis. All patients were treated according to contemporary melanoma management guidelines between 2016 and 2024, with a minimum follow-up of 12 months extending to 2025. Overall survival (OS) and progression-free survival (PFS) analyses were performed in the study cohort. The study included 108 patients with stage II-III malignant melanoma, with a mean age of 56.73 ± 13.51 years. Superficial spreading melanoma was the most frequent histological subtype, followed by nodular and acral melanoma. Most tumors were classified as Clark level IV, with a median Breslow thickness of 3 mm, and ulceration was present in the majority of cases. Lymph node involvement was observed in over half of the patients, and BRAF mutations were identified in 56.48% of cases (the most common variant was V600E). Brisk tumor-infiltrating lymphocytes were significantly more frequent in BRAF wild-type tumors compared with BRAF-mutant tumors. When assessing associations with survival, BRAF mutation status was not found to be an independent predictor. In the multivariate Cox model, TIL status was associated with improved OS (HR 3.33, 95% CI 1.41-7.88, p = 0.006). In addition, in the multivariate analysis, TIL status was also associated with improved PFS (HR 5.23, 95% CI 2.22-12.3, p < 0.001). BRAF wild-type tumors were significantly more likely to exhibit a brisk infiltrate. BRAF mutation status was not found to be an independent predictor of survival. TIL status remained significantly associated with OS and PFS in multivariable analysis.