231 183

Cited 9 times in

Epithelioid hemangioendotheliomas with TFE3 gene translocations are compossible with CAMTA1 gene rearrangements.

Authors
 Seok Joo Lee  ;  Woo Ick Yang  ;  Woo-Suk Chung  ;  Sang Kyum Kim 
Citation
 ONCOTARGET , Vol.7(7) : 7480-7488, 2016 
Journal Title
 ONCOTARGET 
Issue Date
2016
MeSH
Adult ; Aged ; Aged, 80 and over ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Biomarkers, Tumor/genetics* ; Calcium-Binding Proteins/genetics* ; Female ; Follow-Up Studies ; Gene Rearrangement* ; Hemangioendothelioma, Epithelioid/genetics* ; Hemangioendothelioma, Epithelioid/pathology ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Neoplasm Staging ; Oncogene Proteins, Fusion/genetics* ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Trans-Activators/genetics* ; Translocation, Genetic/genetics* ; Young Adult
Keywords
CAMTA1 ; Pathology Section ; TFE3 ; WWTR1 ; YAP1 ; epithelioid hemangioendothelioma
Abstract
Epithelioid hemangioendotheliomas (EHEs) are vascular tumors of intermediate malignancy that can undergo high-grade malignant transformations. EHEs have been characterized by tumor-specific WW domain-containing transcription regulator 1(WWTR1)-calmodulin-binding transcription activator 1 (CAMTA1) translocations, and recently, a novel Yes-associated protein 1 (YAP1)-transcription factor E3 (TFE3) gene fusion was identified in EHEs. In this study, we examined the expression levels of TFE3 and CAMTA1 via immunohistochemical staining and identified chromosomal alterations using fluorescence in situ hybridization (FISH) assays and RT-PCR tests. Although all of the EHEs were CAMTA1-positive in immunohistochemical staining, only five out of 18 EHEs (27.78%) positively expressed nuclear TFE3. The five TFE3-positive EHEs exhibited TFE3 gene break-apart in FISH assays. YAP1-TFE3 gene fusions were confirmed by RT-PCR. Interestingly, we observed CAMTA1 gene break-apart in all of the five TFE3-positive EHEs via FISH assays, and four out of the five TFE3-positive EHEs exhibited WWTR1-CAMTA1 gene fusions via RT-PCR. These results indicate that these two chromosomal alterations are not mutually exclusive but compossible in EHEs. Finally, primary tumor sites in TFE3-positive EHEs consistently contained single masses (P = 0.0359) with larger sizes (P = 0.0550) compared to TFE3-negative EHEs. Similar to previous reports, we observed well-formed vessels more frequently in TFE3-positive EHEs than in TFE3-negative EHEs (P = 0.0441). In addition, TFE3-positive EHEs tended to more frequently demonstrate high-grade nuclear atypia (P = 0.0654) and hypercellularity (P=0.0987) than TFE3-negative EHEs. Thus, we have now established two clinically distinct subgroups of EHEs: TFE3-positive and TFE3-negative EHEs.
Files in This Item:
T201601268.pdf Download
DOI
10.18632/oncotarget.7060
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sang Kyum(김상겸) ORCID logo https://orcid.org/0000-0003-0768-9923
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146764
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse