Different expression of BRAFV600E, ALK and PD-L1 in melanoma in children and adolescents: a nationwide retrospective study in Finland in 1990–2014

Pediatric melanoma may have a different biological background and more favorable prognosis compared with melanoma in adults. The aim of this study was to investigate melanoma in children and adolescents in the Finnish population in terms of incidence, clinical course, treatment, prognosis and BRAFV600E-, ALK- and PD-L1-positivity of the primary tumors.
Primary tumor samples and clinical records of all patients aged 0-19 years diagnosed with cutaneous melanoma in Finland in 1990–2014 were collected using the Finnish Cancer Registry database, Finnish hospitals and private pathology laboratories. BRAFV600E, ALK and PD-L1 were analyzed from 54 primary tumors and BRAFV600E from six metastasis samples.
A total of 122 patients diagnosed with cutaneous melanoma were retrieved from the Cancer Registry database. The primary tumor samples of 73 patients were obtained for the review, and 56 cases were included in the study. The incidence of pediatric melanoma increased from 0.02 to 0.1/100 000 during the period 1990–2014. Spitzoid melanoma was the most common subtype (66%). The 10-year cancer-specific survival (CSS) was 88.7% in all patients. The 10-year-CSS did not differ in SLNB-positive or -negative groups. BRAFV600E was positive in 48%, ALK in 9% and PD-L1 in 2% of the tumors. BRAFV600E mutation was associated with 83% of melanoma deaths.
Young melanoma patients had more favorable prognosis and a different staining profile for BRAFV600E, ALK, and PD-L1 in primary tumor than reported in adults. SLNB status was not an indicator for survival. BRAFV600E-positive patients have worse prognosis and could benefit from surveillance and treatment similarly to adults.

与成人黑色素瘤相比，儿童黑色素瘤（Pediatric melanoma）可能具有独特的生物学背景与更良好的预后。本研究旨在针对芬兰人群中的儿童及青少年黑色素瘤，从发病率、临床病程、治疗方案、预后情况，以及原发肿瘤的BRAFV600E、ALK和PD-L1表达阳性特征展开系统性探究。
本研究依托芬兰癌症登记数据库、芬兰各级医院及私立病理实验室，收集了1990年至2014年间芬兰境内所有确诊为皮肤黑色素瘤的0至19岁患者的原发肿瘤样本与临床诊疗记录。研究团队对54份原发肿瘤样本完成了BRAFV600E、ALK及PD-L1检测，并对6份转移瘤样本开展了BRAFV600E突变检测。
研究人员从癌症登记数据库中共检索到122例确诊皮肤黑色素瘤的患者。其中73例患者的原发肿瘤样本被纳入回顾性分析，最终56例病例纳入本研究范畴。1990年至2014年间，儿童黑色素瘤的发病率从0.02/10万攀升至0.1/10万。Spitz型黑色素瘤（Spitzoid melanoma）为最常见的病理亚型，占比达66%。所有患者的10年癌症特异性生存率（Cancer-Specific Survival, CSS）为88.7%。前哨淋巴结活检（Sentinel Lymph Node Biopsy, SLNB）阳性与阴性患者的10年CSS无显著差异。受试肿瘤样本中，BRAFV600E阳性率为48%，ALK阳性率为9%，PD-L1阳性率为2%。BRAFV600E突变与83%的黑色素瘤死亡病例相关。
相较于成人黑色素瘤患者，年轻黑色素瘤患者的预后更佳，且其原发肿瘤的BRAFV600E、ALK及PD-L1染色表达特征与成人存在显著差异。SLNB状态无法作为生存预后的独立预测指标。BRAFV600E阳性患者的预后更差，此类患者可参考成人患者的诊疗方案，接受针对性监测与治疗。