PMID- 26840265
OWN - NLM
STAT- MEDLINE
DCOM- 20161221
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 7
DP  - 2016 Feb 16
TI  - Epithelioid hemangioendotheliomas with TFE3 gene translocations are compossible 
      with CAMTA1 gene rearrangements.
PG  - 7480-8
LID - 10.18632/oncotarget.7060 [doi]
AB  - 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.
FAU - Lee, Seok Joo
AU  - Lee SJ
AD  - Department of Pathology, Yonsei University Medical Center, Seoul, South Korea.
FAU - Yang, Woo Ick
AU  - Yang WI
AD  - Department of Pathology, Yonsei University Medical Center, Seoul, South Korea.
FAU - Chung, Woo-Suk
AU  - Chung WS
AD  - Department of Diagnostic Radiology, Konyang University Hospital, Daejeon, South 
      Korea.
FAU - Kim, Sang Kyum
AU  - Kim SK
AD  - Department of Pathology, Yonsei University Medical Center, Seoul, South Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CAMTA1 protein, human)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (RNA, Messenger)
RN  - 0 (TFE3 protein, human)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*genetics
MH  - Biomarkers, Tumor/*genetics
MH  - Calcium-Binding Proteins/*genetics
MH  - Female
MH  - Follow-Up Studies
MH  - *Gene Rearrangement
MH  - Hemangioendothelioma, Epithelioid/*genetics/pathology
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Prognosis
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Retrospective Studies
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Trans-Activators/*genetics
MH  - Translocation, Genetic/*genetics
MH  - Young Adult
PMC - PMC4884933
OTO - NOTNLM
OT  - CAMTA1
OT  - Pathology Section
OT  - TFE3
OT  - WWTR1
OT  - YAP1
OT  - epithelioid hemangioendothelioma
COIS- CONFLICTS OF INTERESTS The authors declare that they have no conflicts of 
      interest in the article.
EDAT- 2016/02/04 06:00
MHDA- 2016/12/22 06:00
PMCR- 2016/02/16
CRDT- 2016/02/04 06:00
PHST- 2015/09/02 00:00 [received]
PHST- 2016/01/21 00:00 [accepted]
PHST- 2016/02/04 06:00 [entrez]
PHST- 2016/02/04 06:00 [pubmed]
PHST- 2016/12/22 06:00 [medline]
PHST- 2016/02/16 00:00 [pmc-release]
AID - 7060 [pii]
AID - 10.18632/oncotarget.7060 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Feb 16;7(7):7480-8. doi: 10.18632/oncotarget.7060.