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Metastatic melanoma of unknown primary resembles the genotype of cutaneous melanomas.

BACKGROUND
Although 90% of all melanomas are of cutaneous origin, some patients present with melanoma metastases of unknown origin (MUP). Commonly, in these patients an extensive search for the primary tumor is carried out. In the past, genetic analyses have shown substantial differences in pathogenetic mutations among cutaneous, acral and mucosal melanomas. The aim of this study was to assess the mutational status of MUP in order to better characterize the putative origin of the primary tumor and to evaluate potential prognostic factors.


PATIENTS AND METHODS
The medical records of 44 patients with MUP were analyzed and a survival analysis was conducted. In total, 66 paraffin samples of 44 patients were analyzed, and in 15 patients multiple metastases were tested. Mutational analysis of the BRAF, NRAS and KIT genes was carried out.


RESULTS
Twenty-three patients (52.3%) had a mutation in the BRAF gene and 12 patients (23.8%) had a mutation in the NRAS gene. There were neither mutations in the KIT gene. In patients with multiple samples, there was 100% consistency regarding mutational status among the different metastases. The median overall survival (OS) was 86.4 months (39-134). The American Joint Committee on Cancer stage at first diagnosis of metastatic melanoma (stage III versus IV) was significantly associated with OS (P < 0.001), BRAF or NRAS mutation status had no significant prognostic impact on clinical outcomes.


CONCLUSIONS
MUP resembles the genotype of cutaneous melanoma and not that of mucosal melanomas.