PMID- 30489320
OWN - NLM
STAT- MEDLINE
DCOM- 20200109
LR  - 20220716
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 43
IP  - 3
DP  - 2019 Mar
TI  - Novel PLAG1 Gene Rearrangement Distinguishes a Subset of Uterine Myxoid 
      Leiomyosarcoma From Other Uterine Myxoid Mesenchymal Tumors.
PG  - 382-388
LID - 10.1097/PAS.0000000000001196 [doi]
AB  - Genetic alterations in uterine myxoid leiomyosarcoma are unknown. We investigate 
      the clinicopathologic features of 19 uterine tumors previously diagnosed as 
      myxoid leiomyosarcomas in which tumoral RNA was subjected to targeted RNA 
      sequencing. PLAG1, BCOR, BCORL1, HMGA2, and ALK break-apart fluorescence in situ 
      hybridization (FISH) and BCOR, PLAG1, and ALK immunohistochemistry were performed 
      in cases which failed or lacked fusions by sequencing. The diagnosis of myxoid 
      leiomyosarcoma was confirmed in 15 cases after exclusion of 4 tumors with BCOR 
      and ALK rearrangements. These 15 patients presented at a median age of 50 years 
      with stage I (3), II (2), III (2), and IV (1) tumors, respectively; stage was 
      unknown in 7 cases. Tumor size ranged from 10 to 24 cm. Matrix was myxoid in all 
      tumors and also eosinophilic in 2. Cells were spindled, epithelioid, and both in 
      10, 2, and 3 tumors and showed mild, moderate, and severe nuclear atypia in 3, 8, 
      and 4 tumors, respectively. Mitotic index ranged from <1 to 14/10 HPF, while 
      tumor necrosis was present in 6 (40%). Novel TRPS1-PLAG1 or RAD51B-PLAG1 fusions 
      were detected by sequencing in 4 tumors, 3 of which were also confirmed by FISH. 
      Diffuse PLAG1 expression was seen in 7 tumors, including 4 with PLAG1 
      rearrangement. No morphologic differences were seen among PLAG1 fusion-positive 
      and fusion-negative tumors. No PLAG1, HMGA2, ALK, BCOR, or BCORL1 rearrangements 
      were detected by FISH in 11 tumors. On the basis of sequencing and FISH results, 
      PLAG1 rearrangements resulting in PLAG1 expression underpin ~25% of myxoid 
      leiomyosarcomas and may serve as a useful diagnostic biomarker. 
      Immunohistochemistry, targeted RNA sequencing, and/or FISH may distinguish myxoid 
      leiomyosarcoma from its morphologic mimics.
FAU - Arias-Stella, Javier A 3rd
AU  - Arias-Stella JA 3rd
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Benayed, Ryma
AU  - Benayed R
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 - Young, Robert H
AU  - Young RH
AD  - Department of Pathology, Massachusetts General Hospital and Harvard Medical 
      School, Boston, MA.
FAU - Hoang, Lien N
AU  - Hoang LN
AD  - Department of Pathology, Vancouver General Hospital.
FAU - Lee, Cheng-Han
AU  - Lee CH
AD  - Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada.
FAU - Jungbluth, Achim A
AU  - Jungbluth AA
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Frosina, Denise
AU  - Frosina D
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
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
GR  - P50 CA217694/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 (DNA-Binding Proteins)
RN  - 0 (PLAG1 protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Diagnosis, Differential
MH  - Female
MH  - Gene Rearrangement
MH  - Humans
MH  - Leiomyosarcoma/diagnosis/*genetics
MH  - Middle Aged
MH  - Uterine Neoplasms/diagnosis/*genetics
PMC - PMC6764762
MID - NIHMS1511101
COIS- CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.
EDAT- 2018/11/30 06:00
MHDA- 2020/01/10 06:00
PMCR- 2020/03/01
CRDT- 2018/11/30 06:00
PHST- 2018/11/30 06:00 [pubmed]
PHST- 2020/01/10 06:00 [medline]
PHST- 2018/11/30 06:00 [entrez]
PHST- 2020/03/01 00:00 [pmc-release]
AID - 10.1097/PAS.0000000000001196 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2019 Mar;43(3):382-388. doi: 10.1097/PAS.0000000000001196.