title: Disseminated histiocytoses biomarkers beyond BRAFV600E: frequent expression of PD-L1.
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.
authors.affiliation: Caris Life Sciences, Phoenix, Arizona, USA.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.affiliation: Department of Pathology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
authors.forename: Nurija
authors.initials: N
authors.lastname: Bilalovic
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Palazzo
authors.affiliation: Caris Life Sciences, Phoenix, Arizona, USA.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Bender
authors.affiliation: Caris Life Sciences, Phoenix, Arizona, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Swensen
authors.affiliation: Caris Life Sciences, Phoenix, Arizona, USA.
authors.forename: Sherri Z
authors.initials: SZ
authors.lastname: Millis
authors.affiliation: Department of Pathology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
authors.forename: Semir
authors.initials: S
authors.lastname: Vranic
authors.affiliation: Department of Oncology, Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, Arizona, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Von Hoff
authors.affiliation: 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.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D054740:Dendritic Cell Sarcoma, Follicular / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003713:Dendritic Cells / Q000737:chemistry* / Q000201:enzymology; D031249:Erdheim-Chester Disease / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005819:Genetic Markers; D006644:Histiocytes / Q000737:chemistry* / Q000201:enzymology / Q000473:pathology; D054747:Histiocytic Sarcoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006646:Histiocytosis, Langerhans-Cell / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015618:Histiocytosis, Sinus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D005819:Genetic Markers; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: biomarkers; histiocytoses; immunotherapy; sequencing; targeted therapy