BRAFV600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis
BRAFV600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis
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DOI：
10.1182/blood-2012-06-429597
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发表时间：
2012-09-20
期刊：
影响因子：
20.3
通讯作者：
von Deimling, Andreas
中科院分区：
文献类型：
--
作者：
Sahm, Felix;Capper, David;von Deimling, Andreas
朗格汉斯细胞组织细胞增生症(LCH)是一种临床和组织学异质性疾病。它被归类为反应性炎症或肿瘤性疾病一直存在争议。然而，最近在LCH中发现的频繁的BRAFV600E突变支持后者。携带突变并负责增殖的确切细胞类型仍有待确定。我们在这里应用BRAFV600E突变特异性抗体来检测89例LCH患者皮损中的BRAF突变细胞。我们在89个病变中发现34个(38%)BRAFV600E突变。在BRAFV600E突变的皮损中，大多数共表达S-100和CD1a的细胞含有突变的BRAFV600E蛋白。这些细胞也表达CD14和CD36，而不同部分表达CD207。另一方面，BRAFV600E阳性细胞也表达CD80和CD86。因此，表现出与髓系细胞或去分化朗格汉斯细胞抗原相容的免疫组织化学特征的可变成熟细胞携带BRAFV600E突变。总之，我们通过应用突变特异性标记物来鉴定和鉴定BRAFV600E突变的LCH中的肿瘤细胞，并论证了常规筛查的可行性。(血。2012年；120(12)：E28-E34)
Langerhans cell histiocytosis (LCH) is a clinically and histologically heterogeneous disorder. Its classification as either reactive inflammatory or neoplastic has been a matter of debate. However, the recent finding of frequent BRAFV600E mutations in LCH argues for the latter. The exact cell type that harbors the mutation and is responsible for proliferation remains to be identified. We here apply a BRAFV600E mutation-specific antibody to detect the BRAF mutant cells in lesions from 89 patients with LCH. We found BRAFV600E mutations in 34 of 89 (38%) lesions. In lesions with the BRAFV600E mutation, the majority of cells coexpressing S-100 and CD1a harbored mutant BRAFV600E protein. These cells also expressed CD14 and CD36, whereas various fractions exhibited CD207. On the other hand, CD80 and CD86 expression was also present on BRAFV600E-positive cells. Thus, cells of variable maturation, exhibiting an immunohistochemical profile compatible either with myeloid cell or with dedifferentiated Langerhans cell antigens, carry the BRAFV600E mutation. In conclusion, we identify and characterize the neoplastic cells in LCH with BRAFV600E mutations by applying a mutation-specific marker and demonstrate feasibility for routine screening. (Blood. 2012;120(12):e28-e34)