Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA.
Blood. 2010 Sep 16;116(11):1919-23. doi: 10.1182/blood-2010-04-279083. Epub 2010 Jun 2.
Langerhans cell histiocytosis (LCH) has a broad spectrum of clinical behaviors; some cases are self-limited, whereas others involve multiple organs and cause significant mortality. Although Langerhans cells in LCH are clonal, their benign morphology and their lack (to date) of reported recurrent genomic abnormalities have suggested that LCH may not be a neoplasm. Here, using 2 orthogonal technologies for detecting cancer-associated mutations in formalin-fixed, paraffin-embedded material, we identified the oncogenic BRAF V600E mutation in 35 of 61 archived specimens (57%). TP53 and MET mutations were also observed in one sample each. BRAF V600E tended to appear in younger patients but was not associated with disease site or stage. Langerhans cells stained for phospho-mitogen-activated protein kinase kinase (phospho-MEK) and phospho-extracellular signal-regulated kinase (phospho-ERK) regardless of mutation status. High prevalence, recurrent BRAF mutations in LCH indicate that it is a neoplastic disease that may respond to RAF pathway inhibitors.
朗格汉斯细胞组织细胞增生症（LCH）具有广泛的临床行为；有些病例是自限性的，而有些则涉及多个器官并导致显著的死亡率。尽管 LCH 中的朗格汉斯细胞是克隆性的，但它们良性的形态学以及迄今为止未报道的复发性基因组异常表明 LCH 可能不是肿瘤。在这里，我们使用两种正交技术检测福尔马林固定、石蜡包埋材料中的癌症相关突变，在 61 个存档标本中的 35 个（57%）中鉴定出致癌的 BRAF V600E 突变。每个样本中还观察到 TP53 和 MET 突变。BRAF V600E 倾向于出现在年轻患者中，但与疾病部位或阶段无关。无论是否存在突变，磷酸化丝裂原激活蛋白激酶激酶（磷酸化 MEK）和磷酸化细胞外信号调节激酶（磷酸化 ERK）的朗格汉斯细胞染色。LCH 中高频率、复发性 BRAF 突变表明它是一种可能对 RAF 途径抑制剂有反应的肿瘤性疾病。
