PMID- 30520819
OWN - NLM
STAT- MEDLINE
DCOM- 20200113
LR  - 20200113
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 43
IP  - 4
DP  - 2019 Apr
TI  - MDM2 RNA In Situ Hybridization for the Diagnosis of Atypical Lipomatous Tumor: A 
      Study Evaluating DNA, RNA, and Protein Expression.
PG  - 446-454
LID - 10.1097/PAS.0000000000001199 [doi]
AB  - The distinction of atypical lipomatous tumor/well-differentiated liposarcoma 
      (ALT/WDL) from its benign counterpart, lipoma, may represent a challenge. MDM2 
      DNA amplification is used as the gold standard as MDM2 immunohistochemistry lacks 
      specificity and sensitivity. Herein, we investigate the diagnostic utility of 
      MDM2 RNA in situ hybridization (RNA-ISH) and compare the test with MDM2 
      immunohistochemistry and MDM2 DNA fluorescence in situ hybridization (FISH) in 
      benign and malignant lipomatous neoplasms. We evaluated 109 neoplasms including 
      27 lipomas, 25 spindle cell lipomas, 32 ALTs/WDLs, and 25 dedifferentiated 
      liposarcomas (DDL). The validation cohort included 14 lipoma-like neoplasms that 
      lacked unequivocal features of ALT/WDL and in which MDM2 immunohistochemistry was 
      either equivocal, negative or falsely positive. Immunohistochemistry, automated 
      RNA-ISH and DNA-FISH for MDM2 were performed. Tumors with diffuse nuclear 
      staining or >50 dots per cell on RNA-ISH were considered positive. All lipomas 
      and lipoma variants were negative for RNA-ISH while all ALTs/WDLs and DDLs were 
      positive. Eighty percent (24/30) and 92% (22/24) of ALTs/WDLs and DDLs were 
      positive for MDM2 immunohistochemistry. Lipomas and its variants were negative 
      for MDM2 amplification; 92% and 100% of ALTs/WDLs and DDLs showed MDM2 DNA 
      amplification. The mean percentage of ALT/WDL tumor cells showing MDM2 RNA-ISH 
      positivity was 73% compared with 24% on MDM2 immunohistochemistry. RNA-ISH 
      correctly classified all 10 ALTs/WDLs and all 4 lipomas in the validation cohort. 
      The performance of MDM2 RNA-ISH and MDM2 DNA-FISH are equivalent. MDM2 RNA-ISH 
      can be of diagnostic value in histologically challenging lipomatous neoplasms. 
      The automated MDM2 RNA-ISH assay should allow for more widespread use of MDM2 
      testing and for a more sensitive and specific diagnosis of ALT/WDL.
FAU - Kulkarni, Anupriya S
AU  - Kulkarni AS
AD  - Departments of Pathology.
FAU - Wojcik, John B
AU  - Wojcik JB
AD  - Department of Pathology and Laboratory Medicine Perelman, School of Medicine at 
      the University of Pennsylvania, Philadelphia, PA.
FAU - Chougule, Abhijit
AU  - Chougule A
AD  - Departments of Pathology.
FAU - Arora, Kshitij
AU  - Arora K
AD  - Departments of Pathology.
FAU - Chittampalli, Yashaswini
AU  - Chittampalli Y
AD  - Departments of Pathology.
FAU - Kurzawa, Pawel
AU  - Kurzawa P
AD  - Department of Clinical Pathology, Poznan University of Medical Sciences, Poznan, 
      Poland.
FAU - Mullen, John T
AU  - Mullen JT
AD  - Department of Surgery, Massachusetts General Hospital and Harvard Medical School, 
      Boston, MA.
FAU - Chebib, Ivan
AU  - Chebib I
AD  - Departments of Pathology.
FAU - Nielsen, G Petur
AU  - Nielsen GP
AD  - Departments of Pathology.
FAU - Rivera, Miguel N
AU  - Rivera MN
AD  - Departments of Pathology.
FAU - Ting, David T
AU  - Ting DT
AD  - Medicine, Division of Oncology.
FAU - Deshpande, Vikram
AU  - Deshpande V
AD  - Departments of Pathology.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
RN  - 63231-63-0 (RNA)
RN  - 9007-49-2 (DNA)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Biomarkers, Tumor/*analysis
MH  - DNA/analysis
MH  - Female
MH  - Humans
MH  - In Situ Hybridization/methods
MH  - Liposarcoma/*diagnosis
MH  - Male
MH  - Middle Aged
MH  - Proto-Oncogene Proteins c-mdm2/*analysis
MH  - RNA/analysis
EDAT- 2018/12/07 06:00
MHDA- 2020/01/14 06:00
CRDT- 2018/12/07 06:00
PHST- 2018/12/07 06:00 [pubmed]
PHST- 2020/01/14 06:00 [medline]
PHST- 2018/12/07 06:00 [entrez]
AID - 10.1097/PAS.0000000000001199 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2019 Apr;43(4):446-454. doi: 10.1097/PAS.0000000000001199.