PMID- 30789359
OWN - NLM
STAT- MEDLINE
DCOM- 20200217
LR  - 20200605
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 43
IP  - 5
DP  - 2019 May
TI  - Undifferentiated Uterine Sarcomas Represent Under-Recognized High-grade 
      Endometrial Stromal Sarcomas.
PG  - 662-669
LID - 10.1097/PAS.0000000000001215 [doi]
AB  - Undifferentiated uterine sarcoma is a diagnosis of exclusion with limited 
      molecular genetic data available. Recent recognition of high-grade endometrial 
      stromal sarcomas with diverse genotypes suggests that some tumors classified as 
      undifferentiated uterine sarcomas may represent misdiagnosed high-grade 
      endometrial stromal sarcomas. Archival material from 10 tumors diagnosed as 
      undifferentiated uterine sarcomas in 2009 to 2017 were collected. BCOR 
      immunohistochemistry and fluorescence in situ hybridization (FISH) using 
      break-apart probes flanking BCOR, ZC3H7B, CCNB3, YWHAE, NUTM2, JAZF1, and BCORL1 
      were performed. Tumors lacking or harboring gene rearrangement with no known 
      fusion partner by FISH were subjected to targeted RNA sequencing. Morphology was 
      correlated with FISH and sequencing results. BCOR expression was moderate to 
      strong in >/=50% of cells in 8 tumors, while weak in <5% cells and negative in 2. 
      FISH detected mutually exclusive ZC3H7B-BCOR and YWHAE-NUTM2 fusions in 3 uniform 
      undifferentiated uterine sarcomas; 2 pleomorphic tumors harbored YWHAE 
      rearrangement with no known partner. Targeted RNA sequencing of 5 FISH-negative 
      uniform undifferentiated uterine sarcomas detected BRD8-PHF1 and YWHAE-NUTM2B 
      fusions and BCOR internal tandem duplication in 4 of them. Tumors with 
      YWHAE-NUTM2 fusions and BCOR genetic abnormalities showed morphology 
      characteristic of high-grade endometrial stromal sarcomas. No fusions were 
      detected by sequencing in the tumor with YWHAE rearrangement only by FISH. Most 
      tumors classified as undifferentiated uterine sarcomas represent misdiagnosed 
      high-grade endometrial stromal sarcomas. BCOR expression in >/=50% of cells may 
      help triage tumors for molecular confirmation of high-grade endometrial stromal 
      sarcoma-related genetic abnormalities. Novel YWHAE rearrangements may define a 
      subset of true undifferentiated pleomorphic sarcomas.
FAU - Cotzia, Paolo
AU  - Cotzia P
AD  - Department of Pathology, New York University Langone Medical Center.
FAU - Benayed, Ryma
AU  - Benayed R
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Mullaney, Kerry
AU  - Mullaney K
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Oliva, Esther
AU  - Oliva E
AD  - Department of Pathology, Massachusetts General Hospital and Harvard Medical 
      School, Boston, MA.
FAU - Felix, Ana
AU  - Felix A
AD  - Department of Pathology, Instituto Portugues de Oncologia de Lisboa Francisco 
      Gentil, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal.
FAU - Ferreira, Joana
AU  - Ferreira J
AD  - Department of Pathology, Instituto Portugues de Oncologia de Lisboa Francisco 
      Gentil, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal.
FAU - Soslow, Robert A
AU  - Soslow RA
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Antonescu, Cristina R
AU  - Antonescu CR
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Ladanyi, Marc
AU  - Ladanyi M
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Chiang, Sarah
AU  - Chiang S
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Aged
MH  - Biomarkers, Tumor/analysis/genetics
MH  - Boston
MH  - *Cell Differentiation
MH  - Diagnosis, Differential
MH  - Endometrial Neoplasms/chemistry/genetics/*pathology
MH  - Female
MH  - Gene Fusion
MH  - Gene Rearrangement
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - New York City
MH  - Phenotype
MH  - Portugal
MH  - Predictive Value of Tests
MH  - Retrospective Studies
MH  - Sarcoma, Endometrial Stromal/chemistry/genetics/*pathology
MH  - Uterine Neoplasms/chemistry/genetics/*pathology
PMC - PMC6764763
MID - NIHMS1533009
EDAT- 2019/02/23 06:00
MHDA- 2020/02/18 06:00
PMCR- 2020/05/01
CRDT- 2019/02/22 06:00
PHST- 2019/02/23 06:00 [pubmed]
PHST- 2020/02/18 06:00 [medline]
PHST- 2019/02/22 06:00 [entrez]
PHST- 2020/05/01 00:00 [pmc-release]
AID - 10.1097/PAS.0000000000001215 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2019 May;43(5):662-669. doi: 10.1097/PAS.0000000000001215.