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Clinicopathological features and clinical outcomes associated with TP53 and BRAF N on‐ V 600 mutations in cutaneous melanoma patients
Author(s) -
Kim Dae Won,
Haydu Lauren E.,
Joon Aron Y.,
Bassett Roland L.,
Siroy Alan E.,
Tetzlaff Michael T.,
Routbort Mark J.,
Amaria Rodabe N.,
Wargo Jennifer A.,
McQuade Jennifer L.,
Kemnade Jan,
Hwu Patrick,
Woodman Scott E.,
Roszik Jason,
Kim Kevin B.,
Gershenwald Jeffrey E.,
Lazar Alexander J.,
Davies Michael A.
Publication year - 2017
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.30463
Subject(s) - medicine , neuroblastoma ras viral oncogene homolog , ipilimumab , melanoma , oncology , cohort , univariate analysis , disease , primary tumor , cancer , stage (stratigraphy) , multivariate analysis , metastasis , cancer research , immunotherapy , biology , paleontology , colorectal cancer , kras
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. © 2016 American Cancer Society .