PMID- 27428733
OWN - NLM
STAT- MEDLINE
DCOM- 20170719
LR  - 20220331
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 40
IP  - 12
DP  - 2016 Dec
TI  - BCOR Overexpression Is a Highly Sensitive Marker in Round Cell Sarcomas With BCOR 
      Genetic Abnormalities.
PG  - 1670-1678
AB  - With the advent of next-generation sequencing, an increasing number of novel gene 
      fusions and other abnormalities have emerged recently in the spectrum of 
      EWSR1-negative small blue round cell tumors (SBRCTs). In this regard, a subset of 
      SBRCTs harboring either BCOR gene fusions (BCOR-CCNB3, BCOR-MAML3), BCOR internal 
      tandem duplications (ITD), or YWHAE-NUTM2B share a transcriptional signature 
      including high BCOR mRNA expression, as well as similar histologic features. 
      Furthermore, other tumors such as clear cell sarcoma of kidney (CCSK) and 
      primitive myxoid mesenchymal tumor of infancy also demonstrate BCOR ITDs and high 
      BCOR gene expression. The molecular diagnosis of these various BCOR genetic 
      alterations requires an elaborate methodology including custom BAC fluorescence 
      in situ hybridization (FISH) probes and reverse transcription polymerase chain 
      reaction assays. As these tumors show high level of BCOR overexpression 
      regardless of the genetic mechanism involved, either conventional gene fusion or 
      ITD, we sought to investigate the performance of an anti-BCOR monoclonal antibody 
      clone C-10 (sc-514576) as an immunohistochemical marker for sarcomas with BCOR 
      gene abnormalities. Thus we assessed the BCOR expression in a pathologically and 
      genetically well-characterized cohort of 25 SBRCTs, spanning various BCOR-related 
      fusions and ITDs and YWHAE-NUTM2B fusion. In addition, we included related 
      pathologic entities such as 8 CCSKs and other sarcomas with BCOR gene fusions. As 
      a control group we included 20 SBRCTs with various (non-BCOR) genetic 
      abnormalities, 10 fusion-negative SBRCTs, 74 synovial sarcomas, 29 
      rhabdomyosarcomas, and other sarcoma types. In addition, we evaluated the same 
      study group for SATB2 immunoreactivity, as these tumors also showed SATB2 mRNA 
      upregulation. All SBRCTs with BCOR-MAML3 and BCOR-CCNB3 fusions, as well as most 
      with BCOR ITD (93%), and all CCSKs showed strong and diffuse nuclear BCOR 
      immunoreactivity. Furthermore, all SBRCTs with YWHAE-NUTM2B also were positive. 
      SATB2 stain was also positive in tumors with YWHAE-NUTM2B, BCOR-MAML3, BCOR ITD 
      (75%), BCOR-CCNB3 (71%), and a subset of CCSKs (33%). In conclusion, BCOR 
      immunohistochemical stain is a highly sensitive marker for SBRCTs and CCSKs with 
      BCOR abnormalities and YWHAE-rearrangements and can be used as a useful 
      diagnostic marker in these various molecular subsets. SATB2 immunoreactivity is 
      also present in the majority of this group of tumors.
FAU - Kao, Yu-Chien
AU  - Kao YC
AD  - *Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, 
      Taiwan double daggerDepartment of Anatomical Pathology, Chang Gung Memorial Hospital, Chang 
      Gung University College of Medicine, Taoyuan, Taiwan daggerDepartment of Pathology, 
      Memorial Sloan Kettering Cancer Center, New York, NY  section signDepartments of Pathology 
      and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 
       parallelInstitute of Pediatric Research Citta'della Speranza  paragraph signDepartment of Medical and 
      Diagnostic Sciences and Special Therapies, Pathology Unit, University of Padua, 
      Padua, Italy.
FAU - Sung, Yun-Shao
AU  - Sung YS
FAU - Zhang, Lei
AU  - Zhang L
FAU - Jungbluth, Achim A
AU  - Jungbluth AA
FAU - Huang, Shih-Chiang
AU  - Huang SC
FAU - Argani, Pedram
AU  - Argani P
FAU - Agaram, Narasimhan P
AU  - Agaram NP
FAU - Zin, Angelica
AU  - Zin A
FAU - Alaggio, Rita
AU  - Alaggio R
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
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (BCOR protein, human)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Matrix Attachment Region Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SATB2 protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Biomarkers, Tumor/*genetics/metabolism
MH  - Case-Control Studies
MH  - Child
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Infant
MH  - Infant, Newborn
MH  - Kidney Neoplasms/diagnosis/genetics/metabolism/pathology
MH  - Male
MH  - Matrix Attachment Region Binding Proteins/genetics/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - *Oncogene Fusion
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - Repressor Proteins/*genetics/metabolism
MH  - Sarcoma/*diagnosis/genetics/metabolism/pathology
MH  - *Tandem Repeat Sequences
MH  - Transcription Factors/genetics/metabolism
MH  - Young Adult
PMC - PMC5106294
MID - NIHMS792267
EDAT- 2016/07/19 06:00
MHDA- 2017/07/20 06:00
PMCR- 2017/12/01
CRDT- 2016/07/19 06:00
PHST- 2016/07/19 06:00 [pubmed]
PHST- 2017/07/20 06:00 [medline]
PHST- 2016/07/19 06:00 [entrez]
PHST- 2017/12/01 00:00 [pmc-release]
AID - 10.1097/PAS.0000000000000697 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2016 Dec;40(12):1670-1678. doi: 10.1097/PAS.0000000000000697.