Toscano de Mendonça Ullyanov Bezerra, Cernea Claudio Roberto, Matos Leandro Luongo, Monteiro de Araujo Lima Roberto Rego
Department of Head and Neck Surgery, Instituto Nacional do Cancer do Rio de Janeiro, Rio de Janeiro, Brazil.
Department of Head and Neck Surgery, School of Medicine, University of São Paulo, Sao Paulo-SP, Brazil.
Oncotarget. 2018 May 1;9(33):22886-22894. doi: 10.18632/oncotarget.25094.
Unlike their cutaneous counterparts, head and neck mucosal malignant melanomas (HNMM) are more aggressive, and their prognostic markers have not been fully elucidated. This study, comprising 28 patients with HNMM, aimed to establish the relationship between different mutations and outcome, define the incidence of KIT mutations in HNMM, and identify the correlation among therapeutic options, histopathological findings, demographic data, and clinical response. Clinical analysis included patient characteristics, staging, primary and palliative treatments, and disease-free survival and overall survival (OS). Progression-free survival and OS were analyzed. Paraffin blocks were selected following histologic analyses, enabling DNA extraction. PCR amplification of exons 9, 11, 13, and 17, with different DNA concentrations, was performed. Patients were predominantly females (57%) and aged 27-85 years. All patients underwent surgery; 17 received adjuvant radiotherapy, and recurrences occurred in 82% patients. Oncologic mutations in KIT were found in 7 of 7 tumors, 3 in exon 9, 3 in exon 11, and 1 in exon 13. Predictive factors for recurrence were mitotic rate, vascular invasion, and perineural spread. There were no significant differences in DFS and OS according to KIT mutation. Our study results suggest that some patients might benefit from appropriate targeted therapy with kinase inhibitors.
与皮肤恶性黑色素瘤不同,头颈部黏膜恶性黑色素瘤(HNMM)侵袭性更强,其预后标志物尚未完全阐明。本研究纳入了28例HNMM患者,旨在建立不同突变与预后之间的关系,确定HNMM中KIT突变的发生率,并确定治疗方案、组织病理学结果、人口统计学数据和临床反应之间的相关性。临床分析包括患者特征、分期、主要和姑息治疗以及无病生存期和总生存期(OS)。分析了无进展生存期和OS。在组织学分析后选择石蜡块,以便进行DNA提取。对不同DNA浓度的外显子9、11、13和17进行PCR扩增。患者以女性为主(57%),年龄在27 - 85岁之间。所有患者均接受了手术;17例接受了辅助放疗,82%的患者出现复发。在7例肿瘤中的7例发现了KIT的肿瘤突变,外显子9中有3例,外显子11中有3例,外显子13中有1例。复发的预测因素为有丝分裂率、血管侵犯和神经周围扩散。根据KIT突变情况,DFS和OS无显著差异。我们的研究结果表明,一些患者可能从适当的激酶抑制剂靶向治疗中获益。