Mutation status among patients with sinonasal mucosal melanoma and its impact on survival

Abstract

Background:Sinonasal mucosal melanoma (SNMM) comprises <1% of all melanomas and lacks well-characterised molecular markers. Our aim was to determine the frequencies of common mutations and examine their utility as molecular markers in a large series of primary SNMMs.Methods:SNMM patients seen at our institution from August 1991 through July 2016 were identified. Genomic DNA was extracted from 66 formalin-fixed paraffin-embedded tumours and screened for mutations by direct sequencing. We investigated the association of mutations with clinicopathological features and survival outcomes.Results:Overall, 41% (27 out of 66) of the SNMMs harboured mutations. BRAF and KIT mutations were identified in 8% (five patients) and 5% (three patients) of SNMMs, respectively, whereas NRAS mutations were detected in 30% (20 patients) of SNMMs. Mutation rates in these oncogenes were similar between SNMMs located in the paranasal sinuses and those in the nasal cavity (30% and 13%, respectively, P=0.09). In a multivariate analysis, patients with negative margins had significantly better overall survival (hazard ratio 5.43, 95% confidence interval 1.44–21.85, P=0.01) and disease-specific survival (hazard ratio 21.9, 95% confidence interval 3.71–180, P=0.0004). The mutation status of the tumours showed no association with survival outcomes.Conclusions:In SNNM, mutation status does not affect survival outcomes, but NRAS mutations are relatively frequent and could be targeted in this disease by MEK inhibitors.

CD117 immunoexpression in oral and sinonasal mucosal melanoma does not correlate with somatic driver mutations in the MAPK pathway

“…Likewise, the low prevalence of BRAF mutations in these samples (6.6%) is similar to the 7% and 8% reported by Buery et al and Amit et al in a series from oral and sinonasal melanomas, respectively. Other studies from Italy and Brazil have reported slightly higher frequencies of BRAF mutation in sinonasal (36%) and oral samples (21%) .…”

“…The 4.2% prevalence of KIT mutations in our samples agrees with the minimum value of the range of frequencies previously reported in SNM (4% to 12.5%) but is inferior to the 15% and 27% reported in OM and the 25.9% of other POSNM series . An intriguing finding of this series is the low frequency of KIT mutations (4.2%), despite simultaneously high C‐KIT protein expression.…”

“…Studies conducted in head and neck melanoma from different ethnic and geographic populations have shown NRAS mutation rates from 14% to 30% and comparable rates described in cutaneous tumours (18%‐20%) . Interestingly, the NRAS mutations observed at codon Q61 have been scarcely reported in other series .…”

“…The anatomical site of the tumour could partially explain the different frequencies of KIT mutations between mucosal melanomas since higher rates among vulvovaginal cases have been reported compared to POSNM cases . This might be linked with the potential of neural crest cells to differentiate in melanocytes or could also be associated with ethnic origins, as it is found at a higher frequency in mucosal melanomas among Asiatic compared to Caucasian patients …”

Prognostic factors in 161 patients with mucosal melanoma: a study of German Central Malignant Melanoma Registry

“…To date, only a few studies have evaluated the effect of mutations on mucosal melanoma survival, and the results have been inconsistent. 17,29,30 In our cohort, no statistically significant difference in OS time was detected between the patients with mutations and without mutations.…”