Clinicopathological features and clinical outcomes associated with TP53 and BRAF^{N on- V 600} mutations in cutaneous melanoma patients

BACKGROUND: BRAF^V600, NRAS, TP53, and BRAF^Non-V600 are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAF^V600 and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAF^Non-V600 mutations. METHODS: This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanoma patients who had undergone clinically indicated molecular testing (n = 926). RESULTS: The prevalence of BRAF^V600, NRAS, TP53, and BRAF^Non-V600 mutations was 43%, 21%, 19%, and 7%, respectively. The presence of a TP53 mutation was associated with older age (P =.019), a head and neck primary tumor site (P =.0001), and longer overall survival (OS) from the diagnosis of stage IV disease in univariate (P =.039) and multivariate analyses (P =.015). BRAF^Non-V600 mutations were associated with older age (P =.005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAF^Non-V600 mutations correlated significantly with OS with frontline ipilimumab treatment, and the TP53 status was not significantly associated with outcomes with frontline BRAF inhibitor therapy. Eleven patients with BRAF^Non-V600 mutations were treated with a BRAF inhibitor. Three patients were not evaluable for a response because of treatment cessation for toxicities; the remaining patients had disease progression as the best response to therapy. CONCLUSIONS: These results add to the understanding of the clinical features associated with TP53 and BRAF^Non-V600 mutations in advanced cutaneous melanoma patients, and they support the rationale for evaluating the prognostic significance of TP53 in other cohorts of melanoma patients. Cancer 2017;123:1372–1381.