Research Papers:

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

Zoran Gatalica _, Nurija Bilalovic, Juan P. Palazzo, Ryan P. Bender, Jeffrey Swensen, Sherri Z. Millis, Semir Vranic, Daniel Von Hoff, Robert J. Arceci

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Oncotarget. 2015; 6:19819-19825. doi: 10.18632/oncotarget.4378

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Zoran Gatalica1, Nurija Bilalovic2, Juan P. Palazzo3, Ryan P. Bender1, Jeffrey Swensen1, Sherri Z. Millis1, Semir Vranic2, Daniel Von Hoff4 and Robert J. Arceci5

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

Correspondence to:

Zoran Gatalica, email:

Keywords: histiocytoses, biomarkers, sequencing, targeted therapy, immunotherapy

Received: May 22, 2015 Accepted: May 29, 2015 Published: June 08, 2015


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.

Author Information

Zoran Gatalica
Primary Contact  _

Nurija Bilalovic

Juan P. Palazzo

Ryan P. Bender

Jeffrey Swensen

Sherri Z. Millis

Semir Vranic

Daniel Von Hoff

Robert J. Arceci

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