PMID- 33346147
OWN - NLM
STAT- MEDLINE
DCOM- 20220330
LR  - 20220330
IS  - 1943-7811 (Electronic)
IS  - 1525-1578 (Linking)
VI  - 23
IP  - 3
DP  - 2021 Mar
TI  - A Rapid and Cost-Effective Gene Expression Assay for the Diagnosis of 
      Well-Differentiated and Dedifferentiated Liposarcomas.
PG  - 274-284
LID - S1525-1578(20)30586-9 [pii]
LID - 10.1016/j.jmoldx.2020.11.011 [doi]
AB  - Histologic examination neither reliably distinguishes benign lipomas from 
      atypical lipomatous tumor/well-differentiated liposarcoma, nor dedifferentiated 
      liposarcoma from other pleomorphic sarcomas, entities with different prognoses 
      and management. Molecular confirmation of pathognomonic 12q13-15 amplifications 
      leading to MDM2 overexpression is a diagnostic gold standard. Currently the most 
      commonly used assay for this purpose is fluorescence in situ hybridization 
      (FISH), but this is labor intensive. This study assessed whether newer 
      NanoString-based technology could allow for more rapid and cost-efficient 
      diagnosis of liposarcomas on standard formalin-fixed tissues through gene 
      expression. Leveraging large-scale transcriptome data from The Cancer Genome 
      Atlas, 20 genes were identified, most from the 12q13-15 amplicon, that 
      distinguish dedifferentiated liposarcoma from other sarcomas and can be measured 
      within a single NanoString assay. Using 21 cases of histologically ambiguous 
      low-grade adipocytic tumors with available MDM2 amplification status, a machine 
      learning-based analytical pipeline was built that assigns a given sample as 
      negative or positive for liposarcoma based on quantitative gene expression. The 
      effectiveness of the assay was validated on an independent set of 100 sarcoma 
      samples (including 40 incident prospective cases), where histologic examination 
      was considered insufficient for clinical diagnosis. The NanoString assay had a 
      93% technical success rate, and an accuracy of 97.8% versus an MDM2 amplification 
      FISH gold standard. NanoString had a considerably faster turnaround time and was 
      cheaper than FISH.
CI  - Copyright (c) 2021 Association for Molecular Pathology and American Society for 
      Investigative Pathology. Published by Elsevier Inc. All rights reserved.
FAU - Wang, Xiu Q
AU  - Wang XQ
AD  - Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, 
      Canada; Genetic Pathology Evaluation Centre, Department of Pathology and 
      Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, 
      Canada.
FAU - Wang, Xue Q
AU  - Wang XQ
AD  - Genetic Pathology Evaluation Centre, Department of Pathology and Laboratory 
      Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
FAU - Hsu, Anika T Y W
AU  - Hsu ATYW
AD  - Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, 
      Canada; Genetic Pathology Evaluation Centre, Department of Pathology and 
      Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, 
      Canada.
FAU - Goytain, Angela
AU  - Goytain A
AD  - Genetic Pathology Evaluation Centre, Department of Pathology and Laboratory 
      Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
FAU - Ng, Tony L T
AU  - Ng TLT
AD  - Genetic Pathology Evaluation Centre, Department of Pathology and Laboratory 
      Medicine, University of British Columbia, Vancouver, British Columbia, Canada; 
      Department of Pathology and Laboratory Medicine, Vancouver General Hospital, 
      Vancouver, BC, Canada.
FAU - Nielsen, Torsten O
AU  - Nielsen TO
AD  - Genetic Pathology Evaluation Centre, Department of Pathology and Laboratory 
      Medicine, University of British Columbia, Vancouver, British Columbia, Canada; 
      Department of Pathology and Laboratory Medicine, Vancouver General Hospital, 
      Vancouver, BC, Canada. Electronic address: torsten@mail.ubc.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201217
PL  - United States
TA  - J Mol Diagn
JT  - The Journal of molecular diagnostics : JMD
JID - 100893612
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - *Biomarkers, Tumor
MH  - Cost-Benefit Analysis
MH  - *Gene Expression
MH  - Gene Expression Profiling
MH  - Genetic Testing/economics/*methods/standards
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lipoma/diagnosis/genetics
MH  - Liposarcoma/*diagnosis/*genetics
MH  - Reproducibility of Results
EDAT- 2020/12/22 06:00
MHDA- 2022/03/31 06:00
CRDT- 2020/12/21 08:45
PHST- 2020/06/25 00:00 [received]
PHST- 2020/10/26 00:00 [revised]
PHST- 2020/11/17 00:00 [accepted]
PHST- 2020/12/22 06:00 [pubmed]
PHST- 2022/03/31 06:00 [medline]
PHST- 2020/12/21 08:45 [entrez]
AID - S1525-1578(20)30586-9 [pii]
AID - 10.1016/j.jmoldx.2020.11.011 [doi]
PST - ppublish
SO  - J Mol Diagn. 2021 Mar;23(3):274-284. doi: 10.1016/j.jmoldx.2020.11.011. Epub 2020 
      Dec 17.