Distinguishing Clinicopathologic Features of Patients with V600E and V600K BRAF-mutant Metastatic Melanoma
Menée sur 308 patients australiens atteints d'un mélanome métastatique, cette étude prospective évalue, en fonction de l'âge des patients, la présence de diverses mutations du gène BRAF (V600E, V600K, ...) lors du diagnostic et leur association avec l'évolution de la maladie
Purpose: Certain clinicopathologic features correlate with BRAF mutation status in melanoma including younger age and primary subtype. This study sought to determine the BRAF mutation status by age-decade, and whether BRAF-mutant genotypes correlated with clinicopathologic features and outcome in patients with metastatic melanoma. Experimental Design: A prospectively assembled cohort of Australian patients were followed from diagnosis of metastatic melanoma (n=308). Clinicopathologic variables were correlated with BRAF mutational status, genotype, and survival. Results: Forty-six percent of patients had a BRAF mutation; 73% V600E, 19% V600K, and 8% other genotypes. An inverse relationship existed between BRAF mutation prevalence and age-decade (P less than 0.001). All patients less than 30 years and only 25% (greater than or equal to)70 years had BRAF-mutant melanoma. Amongst BRAF-mutant melanoma, the frequency of non-V600E genotypes (including V600K) increased with increasing age. Non-V600E genotypes comprized less than 20% in patients less than 50yrs, and greater than 40% in those (greater than or equal to)70yrs. A higher degree of cumulative sun-induced damage correlated with V600K but not V600E melanoma (P=0.002). The disease-free interval from diagnosis of primary melanoma to first distant metastasis was shorter for patients with V600K compared with V600E melanoma (17.4 v 39.2 months, P=0.048), with no difference in survival thereafter. In patients BRAF tested at diagnosis of metastatic melanoma, one year survival from diagnosis of metastasis was significantly longer for patients with BRAF-mutant melanoma treated with an inhibitor (83%), than those not treated with an inhibitor (29%, P less than 0.001), or patients with BRAF wild-type melanoma (37%, P less than 0.001). Conclusions: Different genotypes exist within BRAF-mutant metastatic melanoma, representing biologically and clinically discrete subtypes, suggesting distinct etiology and behavior.
Clinical Cancer Research , résumé, 2012