PMID- 35074968
OWN - NLM
STAT- MEDLINE
DCOM- 20220223
LR  - 20220430
IS  - 0974-5130 (Electronic)
IS  - 0377-4929 (Linking)
VI  - 65
IP  - 1
DP  - 2022 Jan-Mar
TI  - Detection of MDM2 gene amplification on tissue microarray-based Fluorescence 
      In-Situ Hybridization (FISH) in well-differentiated and dedifferentiated 
      liposarcomas, displaying a wide morphological spectrum: A validation study at a 
      tertiary cancer referral centre.
PG  - 65-75
LID - 10.4103/IJPM.IJPM_1238_20 [doi]
AB  - BACKGROUND: Liposarcomas including atypical lipomatous tumors 
      (ALT)/well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas 
      (DDLPSs) display a histomorphological spectrum with their several diagnostic 
      mimics. Murine double minute 2(MDM2) gene amplification characterizes ALT/WDLPS 
      and DDLPS. Presently, there is no documented study from our subcontinent on the 
      validation of MDM2 gene testing in these tumors. MATERIAL AND METHODS: 
      Twenty-eight cases, diagnosed as ALT/WDLPS (n = 5) and DDLPSs (n = 23), along 
      with 10 other tumors were tested for MDM2 gene amplification, using fluorescence 
      in situ hybridization (FISH) on tissue microarrays (TMAs). Fourteen cases, 
      diagnosed as ALT/WDLPS and DDLPS, along with 49 other tumors were tested for MDM2 
      immunostaining. Twenty tumors were tested for p16(INK4a) immunostaining. RESULTS: 
      FISH was interpretable in 25 (89.2%) cases. Among the 20 cases diagnosed as 
      DDLPSs, 19 displayed MDM2 gene amplification. Among the 5 cases diagnosed as 
      ALT/WDLPS, four showed MDM2 gene amplification. Finally, 19 cases were confirmed 
      as DDLPS and 4 as ALT/WDLPS. Furthermore, 7/19 cases confirmed as DDLPS and all 4 
      cases as ALT/WDLPS tested for MDM2 immunostaining, displayed its diffuse 
      immunoexpression, while a single case of DDLPS showed its focal immunostaining. 
      None of the 49 control cases displayed diffuse MDM2 immunoexpression. ALL 16 
      DDLPSs and 4 cases of ALT/WDLPS displayed p16(INK4a) immunostaining. The 
      sensitivity for diffuse MDM2 immunostaining was 87.5% in cases of DDLPS, 100% in 
      ALT/WDLPS, and specificity was 100%. The sensitivity for MDM2 gene amplification 
      was 94.7% in cases of DDLPS and 100% in cases of ALT/WDLPS. The sensitivity for 
      p16(INK4a) was 100%. CONCLUSION: This constitutes the first sizable study on MDM2 
      testing in ALT/WDLPS and DDLPS from our subcontinent using TMAs. MDM2 gene 
      amplification testing continues as the diagnostic gold standard for ALTs/WDLPSs 
      and DDLPSs and is useful in cases of diagnostic dilemmas. Diffuse MDM2 (IF2 
      clone) and p16(INK4a) immunostaining, together seem useful for triaging cases for 
      FISH.
FAU - Rekhi, Bharat
AU  - Rekhi B
AD  - Department of Surgical Pathology; Division of Molecular Pathology and 
      Translational Medicine, Homi Bhabha National Institute (HBNI) University, Mumbai, 
      Maharashtra, India.
FAU - Karnik, Nupur
AU  - Karnik N
AD  - Department of Surgical Pathology; Division of Molecular Pathology and 
      Translational Medicine, Homi Bhabha National Institute (HBNI) University, Mumbai, 
      Maharashtra, India.
FAU - Agrawal, Radhika
AU  - Agrawal R
AD  - Department of Surgical Pathology, Homi Bhabha National Institute (HBNI) 
      University, Mumbai, Maharashtra, India.
FAU - Shetty, Omshree
AU  - Shetty O
AD  - Department of Division of Molecular Pathology and Translational Medicine, Homi 
      Bhabha National Institute (HBNI) University, Mumbai, Maharashtra, India.
FAU - Patkar, Shraddha
AU  - Patkar S
AD  - Department of Surgical Oncology, Gastrointestinal, Retroperitoneum, Tata Memorial 
      Hospital, Homi Bhabha National Institute (HBNI) University, Mumbai, Maharashtra, 
      India.
LA  - eng
PT  - Journal Article
PT  - Validation Study
PL  - India
TA  - Indian J Pathol Microbiol
JT  - Indian journal of pathology & microbiology
JID - 7605904
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/genetics
MH  - Cell Dedifferentiation
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Liposarcoma/classification/*genetics
MH  - Male
MH  - Middle Aged
MH  - Nucleic Acid Amplification Techniques/*methods/standards
MH  - Proto-Oncogene Proteins c-mdm2/*genetics
MH  - Soft Tissue Neoplasms/diagnosis/genetics
MH  - Tissue Array Analysis/*methods/standards
OTO - NOTNLM
OT  - Dedifferentiated liposarcoma
OT  - FISH
OT  - MDM2
OT  - liposarcoma
OT  - tissue microarray
COIS- None
EDAT- 2022/01/26 06:00
MHDA- 2022/02/24 06:00
CRDT- 2022/01/25 05:48
PHST- 2022/01/25 05:48 [entrez]
PHST- 2022/01/26 06:00 [pubmed]
PHST- 2022/02/24 06:00 [medline]
AID - IndianJPatholMicrobiol_2022_65_1_65_336054 [pii]
AID - 10.4103/IJPM.IJPM_1238_20 [doi]
PST - ppublish
SO  - Indian J Pathol Microbiol. 2022 Jan-Mar;65(1):65-75. doi: 
      10.4103/IJPM.IJPM_1238_20.