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Oncotarget. 2015 Aug 14;6(23):19819-25.

Disseminated histiocytoses biomarkers beyond BRAFV600E: frequent expression of PD-L1.

Author information

1
Caris Life Sciences, Phoenix, Arizona, USA.
2
Department of Pathology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
3
Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
4
Department of Oncology, Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, Arizona, USA.
5
Department of Child Health, University of Arizona College of Medicine, Phoenix, Ronald Matricaria Institute of Molecular Medicine at Phoenix Children's Hospital, Phoenix, Arizona, USA.

Abstract

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.

KEYWORDS:

biomarkers; histiocytoses; immunotherapy; sequencing; targeted therapy

PMID:
26110571
PMCID:
PMC4637323
DOI:
10.18632/oncotarget.4378
[Indexed for MEDLINE]
Free PMC Article
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