PMID- 28009602
OWN - NLM
STAT- MEDLINE
DCOM- 20170724
LR  - 20181113
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 41
IP  - 4
DP  - 2017 Apr
TI  - EWSR1 Fusions With CREB Family Transcription Factors Define a Novel Myxoid 
      Mesenchymal Tumor With Predilection for Intracranial Location.
PG  - 482-490
LID - 10.1097/PAS.0000000000000788 [doi]
AB  - Recurrent gene fusions involving EWSR1 with members of the cAMP response element 
      binding protein (CREB) family (ATF1 and CREB1) have been reported in a diverse 
      group of tumors including angiomatoid fibrous histiocytoma (AFH), soft tissue and 
      gastrointestinal clear cell sarcoma, primary pulmonary myxoid sarcoma, and 
      hyalinizing clear cell carcinoma of salivary gland. We have recently encountered 
      a group of 5 myxoid mesenchymal tumors positive for EWSR1 fusions with one of the 
      CREB family member (ATF1, CREB1, and CREM), with histologic features distinct 
      from any of the previously described pathologic entities. Tumors occurred in 
      children or young adults (12 to 23 y; mean, 18 y), with equal sex distribution. 
      All except 1 were intracranial (intra-axial, 2; meningeal, 2), whereas 1 was 
      perirectal. Histologically, the tumors were well circumscribed, often lobulated, 
      composed of uniform ovoid to round cells, and arranged in cord-like or reticular 
      structures in a myxoid background. All except 1 displayed unique sunburst 
      amianthoid fibers. Immunohistochemically, tumors were positive for epithelial 
      membrane antigen (5/5; 4 focal, 1 diffuse) and desmin (3/5). A novel EWSR1-CREM 
      fusion was identified by RNA sequencing in the perirectal tumor, which was 
      further confirmed by fluorescence in situ hybridization (FISH) and reverse 
      transcription-polymerase chain reaction (RT-PCR). A second case with similar 
      EWSR1-CREM fusion was identified by RT-PCR and FISH in a meningeal tumor. The 
      remaining cases studied by FISH showed the presence of EWSR1-CREB1 fusion in 2 
      cases and EWSR1-ATF1 in 1. In conclusion, we report a distinct group of myxoid 
      mesenchymal neoplasms occurring in children or young adults with a predilection 
      for intracranial locations. Although the immunoprofile [epithelial membrane 
      antigen (EMA), desmin] and the fusion type raise the possibility of a myxoid AFH, 
      none of the typical histologic findings of AFH were present, suggesting a novel 
      entity.
FAU - Kao, Yu-Chien
AU  - Kao YC
AD  - *Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, 
      Taiwan daggerDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New 
      York, NY double daggerDepartment of Musculoskeletal Pathology, The Royal Orthopaedic Hospital 
      NHS Foundation Trust, Birmingham, UK.
FAU - Sung, Yun-Shao
AU  - Sung YS
FAU - Zhang, Lei
AU  - Zhang L
FAU - Chen, Chun-Liang
AU  - Chen CL
FAU - Vaiyapuri, Sumathi
AU  - Vaiyapuri S
FAU - Rosenblum, Marc K
AU  - Rosenblum MK
FAU - Antonescu, Cristina R
AU  - Antonescu CR
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - P50 CA140146/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CREM protein, human)
RN  - 0 (Calmodulin-Binding Proteins)
RN  - 0 (EWSR1 protein, human)
RN  - 0 (EWSR1-ATF1 fusion protein, human)
RN  - 0 (EWSR1-CREB1 fusion protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (RNA-Binding Protein EWS)
RN  - 0 (RNA-Binding Proteins)
RN  - 135844-64-3 (Cyclic AMP Response Element Modulator)
SB  - IM
MH  - Adolescent
MH  - Biomarkers, Tumor/analysis/*genetics
MH  - Biopsy
MH  - Brain Neoplasms/chemistry/*genetics/pathology
MH  - Calmodulin-Binding Proteins/*genetics
MH  - Child
MH  - Cyclic AMP Response Element Modulator/*genetics
MH  - Female
MH  - *Gene Fusion
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Oncogene Proteins, Fusion/*genetics
MH  - RNA-Binding Protein EWS
MH  - RNA-Binding Proteins/*genetics
MH  - Rectal Neoplasms/chemistry/*genetics/pathology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Analysis, RNA
MH  - Soft Tissue Neoplasms/chemistry/*genetics/pathology
MH  - Stromal Cells/chemistry/pathology
MH  - Young Adult
PMC - PMC5350023
MID - NIHMS829478
COIS- Conflicts of interest: none
EDAT- 2016/12/24 06:00
MHDA- 2017/07/25 06:00
PMCR- 2018/04/01
CRDT- 2016/12/24 06:00
PHST- 2016/12/24 06:00 [pubmed]
PHST- 2017/07/25 06:00 [medline]
PHST- 2016/12/24 06:00 [entrez]
PHST- 2018/04/01 00:00 [pmc-release]
AID - 10.1097/PAS.0000000000000788 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2017 Apr;41(4):482-490. doi: 10.1097/PAS.0000000000000788.