Disseminated histiocytoses biomarkers beyond BRAFV600E: frequent expression of PD-L1
Disseminated histiocytoses biomarkers beyond BRAFV600E: frequent expression of PD-L1
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DOI：
10.18632/oncotarget.4378
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发表时间：
2015-08-14
期刊：
影响因子：
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通讯作者：
Arceci, Robert J.
中科院分区：
文献类型：
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作者：
Gatalica, Zoran;Bilalovic, Nurija;Arceci, Robert J.
组织细胞病是一种罕见的肿瘤，其特征是组织细胞和树突状细胞的原发性积聚和组织浸润。在Erdheim-Chester病（ECD）和朗格汉斯细胞组织细胞增生症（LCH）病例中识别激活BRAFV 600 E突变为BRAF和/或MEK抑制剂治疗提供了基础，但需要额外的治疗选择。采用免疫组化和突变分析法对24例肿瘤性组织细胞疾病（11例肺外LCH、4例ECD、4例结节性Rosai-Dorfman病（RDD）、3例滤泡树突状细胞肉瘤（FDCS）、1例组织细胞肉瘤（HS）和1例母细胞浆细胞样树突状细胞肿瘤（BPDCN））进行分析，以寻找靶向治疗的生物标志物。在4/11例LCH和4/4例ECD病例中检测到BRAF V600 E突变。在HS病例中发现了致病性PTEN基因突变和PTEN蛋白表达缺失。在3/4个ECD、7/8个LCH、3/3个FDCS和1/1个HS中观察到PD-L1表达增加（>= 2 +/>= 5%），研究中使用的2种抗体之间的总体一致性为81%（SP142 vs. MAB 1561克隆）。这些结果首次显示了PD-L1免疫检查点蛋白在这些疾病中的显著表达，这可能为在治疗播散性和/或难治性组织细胞病中添加免疫检查点抑制剂提供了依据。
The histiocytoses are rare tumors characterized by the primary accumulation and tissue infiltration of histiocytes and dendritic cells. Identification of the activating BRAFV600E mutation in Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) cases provided the basis for the treatment with BRAF and/or MEK inhibitors, but additional treatment options are needed. Twenty-four cases of neoplastic histiocytic diseases [11 extrapulmonary LCH, 4 ECD, 4 extranodal Rosai-Dorfman disease (RDD), 3 follicular dendritic cell sarcoma (FDCS), 1 histiocytic sarcoma (HS) and 1 blastic plasmacytoid dendritic cell neoplasm (BPDCN)] were analyzed using immunohistochemical and mutational analysis in search of biomarkers for targeted therapy. BRAF V600E mutations were detected in 4/11 LCH and 4/4 ECD cases. A pathogenic PTEN gene mutation and loss of PTEN protein expression were identified in the case of HS. Increased expression of PD-L1 (>= 2 +/>= 5%) was seen in 3/4 ECD, 7/8 LCH, 3/3 FDCS and 1/1 HS, with overall 81% concordance between 2 antibodies used in the study (SP142 vs. MAB1561 clone). These results show for the first time significant expression of the PD-L1 immune checkpoint protein in these disorders, which may provide rationale for addition of immune check-point inhibitors in treatment of disseminated and/or refractory histiocytoses.