Molecular characterization of epithelioid haemangioendotheliomas identifies novel WWTR1–CAMTA1 fusion variants1. Issue 5 (14th May 2015)

• Record Type: Journal Article
• Authors: Patel, Nimesh R; Salim, Alaa A; Sayeed, Hadi; Sarabia, Stephen F; Hollingsworth, Faith; Warren, Mikako; Jakacky, Jared; Tanas, Munir; Oliveira, Andre M; Rubin, Brian P; Lazar, Alexander J; López‐Terrada, Dolores; Wang, Wei‐Lien
• Is Part Of: Histopathology. Volume 67:Issue 5(2015)
• Page Start: 699
• Page End: 708
• Publication Date: 2015-05-14
• Subjects: Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.12697
• Languages: English
• ISSNs: 0309-0167

Abstract

<abstract abstract-type="main" id="his12697-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="his12697-sec-0001" sec-type="section"> <title>Aims</title> <p>Epithelioid haemangioendothelioma (EHE) is a malignant vascular neoplasm. Subsets have been characterized previously by translocations resulting in either <italic>WWTR1</italic>–<italic>CAMTA1</italic> or <italic>YAP1</italic>–<italic>TFE3</italic> fusion. We sought to develop molecular and immunohistochemical (IHC) assays to aid in the diagnosis and characterization of EHE.</p> </sec> <sec id="his12697-sec-0002" sec-type="section"> <title>Methods and results</title> <p>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 <italic>WWTR1</italic>–<italic>CAMTA1</italic> and <italic>YAP1</italic>–<italic>TFE3</italic> 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 <italic>WWTR1</italic>–<italic>CAMTA1</italic> 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 <italic>WWTR1</italic>–<italic>CAMTA1</italic> fusion. One of 18 informative cases was positive for <italic>YAP1</italic>–<italic>TFE3</italic> fusion and showed strong nuclear TFE3 staining by IHC.</p> </sec> <sec id="his12697-sec-0003" sec-type="section"> <title>Conclusions</title> <p>This study confirms the high incidence of <italic>WWTR1</italic>–<italic>CAMTA1</italic> and <italic>YAP1</italic>–<italic>TFE3</italic> rearrangements in EHE and indicates that the staining pattern for TFE3 IHC is critical for specificity.</p> </sec> </abstract>