title: Molecular characterization of epithelioid haemangioendotheliomas identifies novel WWTR1-CAMTA1 fusion variants.
abstract: OBJECTIVE
  Epithelioid haemangioendothelioma (EHE) is a malignant vascular neoplasm. Subsets have been characterized previously by translocations resulting in either WWTR1-CAMTA1 or YAP1-TFE3 fusion. We sought to develop molecular and immunohistochemical (IHC) assays to aid in the diagnosis and characterization of EHE.
  
  
  RESULTS
  Fifty-two formalin-fixed, paraffin-embedded (FFPE) cases diagnosed between 2002 and 2014 were retrieved from the pathology files of our institutions. Reverse transcription-polymerase chain reaction (RT-PCR) assays were optimized to detect WWTR1-CAMTA1 and YAP1-TFE3 fusion transcripts in FFPE tissue and transcription factor E3 (TFE3) protein accumulation was examined by immunohistochemistry (IHC). RNA was extracted from 33 adequate samples, with more recent cases providing a greater yield of high quality RNA. Fourteen of 18 informative cases were positive for WWTR1-CAMTA1 fusion transcripts, four of which showed higher-grade cytological features termed by some as 'malignant EHE'. Novel in-frame fusion transcripts were identified in four cases by direct sequencing. IHC revealed variable nuclear TFE3 staining in six of 17 cases; three with patchy staining showed WWTR1-CAMTA1 fusion. One of 18 informative cases was positive for YAP1-TFE3 fusion and showed strong nuclear TFE3 staining by IHC.
  
  
  CONCLUSIONS
  This study confirms the high incidence of WWTR1-CAMTA1 and YAP1-TFE3 rearrangements in EHE and indicates that the staining pattern for TFE3 IHC is critical for specificity.
authors: Department of Pathology, Texas Children's Hospital, Houston, TX, USA.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
authors: Nimesh R
authors: NR
authors: Patel
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Alaa A
authors: AA
authors: Salim
authors: Department of Pathology, Texas Children's Hospital, Houston, TX, USA.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
authors: Hadi
authors: H
authors: Sayeed
authors: Department of Pathology, Texas Children's Hospital, Houston, TX, USA.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
authors: Stephen F
authors: SF
authors: Sarabia
authors: Department of Pathology, Texas Children's Hospital, Houston, TX, USA.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
authors: Faith
authors: F
authors: Hollingsworth
authors: Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital, Cincinnati, OH, USA.
authors: Mikako
authors: M
authors: Warren
authors: Department of Pathology, Texas Children's Hospital, Houston, TX, USA.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
authors: Jared
authors: J
authors: Jakacky
authors: Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors: Munir
authors: M
authors: Tanas
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors: Andre M
authors: AM
authors: Oliveira
authors: Pathology and Laboratory Medicine Institute, Cleveland Clinic and the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
authors: Brian P
authors: BP
authors: Rubin
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Alexander J
authors: AJ
authors: Lazar
authors: Department of Pathology, Texas Children's Hospital, Houston, TX, USA.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
authors: Dolores
authors: D
authors: López-Terrada
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Wei-Lien
authors: WL
authors: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics*; D005260:Female; D018323:Hemangioendothelioma, Epithelioid / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D000091102:YAP-Signaling Proteins; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C487554:CAMTA1 protein, human; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion; D010750:Phosphoproteins; C069203:TFE3 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human
keywords: CAMTA1; TFE3; WWTR1; YAP1; epithelioid; haemangioendothelioma; sarcoma; translocation