Amit Moran, Tam Samantha, Abdelmeguid Ahmed S, Roberts Dianna B, Takahashi Yoko, Raza Shaan M, Su Shirley Y, Kupferman Michael E, DeMonte Franco, Hanna Ehab Y
Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, Mansoura University, Mansoura City 77030-4009, Egypt.
Br J Cancer. 2017 Jun 6;116(12):1564-1571. doi: 10.1038/bjc.2017.125. Epub 2017 May 11.
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.
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.
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.
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.
鼻窦黏膜黑色素瘤（SNMM）占所有黑色素瘤的比例不到1%，且缺乏特征明确的分子标志物。我们的目的是确定常见突变的频率，并在一系列原发性SNMM中检验其作为分子标志物的效用。
确定了1991年8月至2016年7月在我们机构就诊的SNMM患者。从66例福尔马林固定石蜡包埋的肿瘤中提取基因组DNA，并通过直接测序筛选突变。我们研究了突变与临床病理特征及生存结果之间的关联。
总体而言，41%（66例中的27例）的SNMM存在突变。BRAF和KIT突变分别在8%（5例患者）和5%（3例患者）的SNMM中被鉴定出来，而NRAS突变在30%（20例患者）的SNMM中被检测到。位于鼻窦的SNMM和鼻腔的SNMM中这些癌基因的突变率相似（分别为30%和13%，P = 0.09）。在多变量分析中，切缘阴性的患者总生存期（风险比5.43，95%置信区间1.44 - 21.85，P = 0.01）和疾病特异性生存期（风险比21.9，95%置信区间3.71 - 180，P = 0.0004）显著更好。肿瘤的突变状态与生存结果无关。
在SNNM中，突变状态不影响生存结果，但NRAS突变相对常见，MEK抑制剂可能对这种疾病有效。
