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

// Zoran Gatalica 1 , Nurija Bilalovic 2 , Juan P. Palazzo 3 , Ryan P. Bender 1 , Jeffrey Swensen 1 , Sherri Z. Millis 1 , Semir Vranic 2 , Daniel Von Hoff 4 and Robert J. Arceci 5 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 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.