PMID- 29553955
OWN - NLM
STAT- MEDLINE
DCOM- 20190715
LR  - 20221207
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 42
IP  - 6
DP  - 2018 Jun
TI  - NTRK Fusions Define a Novel Uterine Sarcoma Subtype With Features of 
      Fibrosarcoma.
PG  - 791-798
LID - 10.1097/PAS.0000000000001055 [doi]
AB  - Tropomyosin receptor kinase (Trk) inhibitors have shown high response rates in 
      patients with tumors harboring NTRK fusions. We identified 4 NTRK fusion-positive 
      uterine sarcomas that should be distinguished from leiomyosarcoma and 
      undifferentiated uterine sarcoma. NTRK rearrangements were detected by 
      fluorescence in situ hybridization (FISH) and/or targeted RNA or DNA sequencing 
      in 4 undifferentiated uterine sarcomas with spindle cell morphology. Because of 
      histologic overlap with leiomyosarcoma, TrkA and pan-Trk immunohistochemistry was 
      performed in 97 uterine leiomyosarcomas. NTRK1 and NTRK3 FISH was performed on 
      tumors with TrkA or pan-Trk staining. We also performed whole transcriptome RNA 
      sequencing of a leiomyosarcoma with TrkA expression and targeted RNA sequencing 
      of 2 additional undifferentiated uterine sarcomas. FISH and/or targeted RNA or 
      DNA sequencing in the study group showed TPM3-NTRK1, LMNA-NTRK1, RBPMS-NTRK3, and 
      TPR-NTRK1 fusions. All tumors were composed of fascicles of spindle cells. 
      Mitotic index was 7 to 30 mitotic figures per 10 high power fields; tumor 
      necrosis was seen in 2 tumors. Desmin, estrogen receptor, and progesterone 
      receptor were negative in all tumors, while pan-Trk was expressed in all tumors 
      with concurrent TrkA staining in 3 of them. TrkA and/or pan-Trk staining was also 
      seen in 6 leiomyosarcomas, but these tumors lacked NTRK fusions or alternative 
      isoforms by FISH or whole transcriptome sequencing. No fusions were detected in 2 
      undifferentiated uterine sarcomas. NTRK fusion-positive uterine spindle cell 
      sarcomas constitute a novel tumor type with features of fibrosarcoma; patients 
      with these tumors may benefit from Trk inhibition. TrkA and pan-Trk expression in 
      leiomyosarcomas is rare and does not correlate with NTRK rearrangement.
FAU - Chiang, Sarah
AU  - Chiang S
AD  - Departments of Pathology.
FAU - Cotzia, Paolo
AU  - Cotzia P
AD  - Departments of Pathology.
FAU - Hyman, David M
AU  - Hyman DM
AD  - Medicine, Gynecologic Medical Oncology Service.
FAU - Drilon, Alexander
AU  - Drilon A
AD  - Medicine, Thoracic Oncology Service.
FAU - Tap, William D
AU  - Tap WD
AD  - Medicine, Sarcoma Medical Oncology Service, Memorial Sloan Kettering Cancer 
      Center, New York, NY.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Departments of Pathology.
FAU - Hechtman, Jaclyn F
AU  - Hechtman JF
AD  - Departments of Pathology.
FAU - Frosina, Denise
AU  - Frosina D
AD  - Departments of Pathology.
FAU - Jungbluth, Achim A
AU  - Jungbluth AA
AD  - Departments of Pathology.
FAU - Murali, Rajmohan
AU  - Murali R
AD  - Departments of Pathology.
FAU - Park, Kay J
AU  - Park KJ
AD  - Departments of Pathology.
FAU - Soslow, Robert A
AU  - Soslow RA
AD  - Departments of Pathology.
FAU - Oliva, Esther
AU  - Oliva E
AD  - Department of Pathology, Massachusetts General Hospital.
AD  - Department of Pathology, Harvard Medical School, Boston, MA.
FAU - Iafrate, A John
AU  - Iafrate AJ
AD  - Department of Pathology, Massachusetts General Hospital.
AD  - Department of Pathology, Harvard Medical School, Boston, MA.
FAU - Benayed, Ryma
AU  - Benayed R
AD  - Departments of Pathology.
FAU - Ladanyi, Marc
AU  - Ladanyi M
AD  - Departments of Pathology.
FAU - Antonescu, Cristina R
AU  - Antonescu CR
AD  - Departments of Pathology.
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 (NTRK1 protein, human)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkC)
SB  - IM
MH  - Adult
MH  - Biomarkers, Tumor/analysis/*genetics
MH  - Diagnosis, Differential
MH  - Female
MH  - Fibrosarcoma/chemistry/*genetics/pathology
MH  - *Gene Fusion
MH  - *Gene Rearrangement
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Leiomyosarcoma/chemistry/*genetics/pathology
MH  - Middle Aged
MH  - Mitotic Index
MH  - Phenotype
MH  - Predictive Value of Tests
MH  - Prospective Studies
MH  - Receptor, trkA/analysis/*genetics
MH  - Receptor, trkC/analysis/*genetics
MH  - Sarcoma/chemistry/*genetics/pathology
MH  - Uterine Neoplasms/chemistry/*genetics/pathology
MH  - Exome Sequencing
PMC - PMC6764747
MID - NIHMS945057
EDAT- 2018/03/20 06:00
MHDA- 2019/07/16 06:00
PMCR- 2019/09/27
CRDT- 2018/03/20 06:00
PHST- 2018/03/20 06:00 [pubmed]
PHST- 2019/07/16 06:00 [medline]
PHST- 2018/03/20 06:00 [entrez]
PHST- 2019/09/27 00:00 [pmc-release]
AID - 10.1097/PAS.0000000000001055 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2018 Jun;42(6):791-798. doi: 10.1097/PAS.0000000000001055.