Stains & CD markers
MDM2

Editorial Board Member: Borislav A. Alexiev, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Jennifer Yoest, M.D.
Navid Sadri, M.D., Ph.D.

Topic Completed: 15 December 2020

Minor changes: 16 June 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: MDM2[TI] free full text[SB] pathology stains

Jennifer Yoest, M.D.
Navid Sadri, M.D., Ph.D.
Page views in 2020: 10,006
Page views in 2021 to date: 7,587
Cite this page: Yoest J, Sadri N. MDM2. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsmdm2.html. Accessed July 31st, 2021.
Definition / general
  • Murine double minute 2
  • Located on 12q15
  • Encodes protein that inhibits p53
  • Amplified in various malignancies
Essential features
  • MDM2 amplified on supernumerary ring or marker chromosomes in many tumors, leading to suppression of p53
  • Common in atypical lipomatous tumor / well differentiated liposarcoma and dedifferentiated liposarcoma; often used to distinguish these entities from mimickers
  • Distinguish low grade osteosarcoma and parosteal osteosarcoma (positive) from benign fibrous and fibro-osseous lesions (negative)
  • Commonly tested by FISH or IHC, also dual color chromogenic in situ hybridization (DISH / CISH); FISH widely accepted as gold standard
Terminology
  • Murine double minute 2
  • Hdm2
  • E3 ubiquitin ligase MDM2
  • MDM2 proto-oncogene
  • p53 binding protein MDM2
Pathophysiology
Clinical features
Interpretation
Uses by pathologists
Prognostic factors
Microscopic (histologic) images

Contributed by Jennifer Yoest, M.D. (source: University of Michigan Virtual Slide Box)
Dedifferentiated liposarcoma

Dedifferentiated liposarcoma

MDM2 IHC in dedifferentiated liposarcoma

MDM2 IHC in dedifferentiated liposarcoma

ALT/WDL

ALT / WDL

MDM2 IHC in ATL/WDL

MDM2 IHC in ATL / WDL

Virtual slides

Images hosted on other servers:

Metastatic dedifferentiated liposarcoma to lung (H&E)

Metastatic dedifferentiated liposarcoma to lung (MDM2 IHC)

Well differentiated liposarcoma (H&E)

Well differentiated liposarcoma (MDM2 IHC)

ALT / WDL (H&E)

ALT / WDL (MDM2 IHC)

Positive staining - normal
Positive staining - disease
Negative staining
Molecular / cytogenetics description
  • FISH: true amplification indicated by increased number of MDM2 probe signals as compared with centromeric chromosome 12 probe (positive cutoff ratio set by lab); polysomy 12 (increased number of both MDM2 and centromeric chromosome 12 signals) seen in other sarcomas, especially with complex karyotype (Virchows Arch 2010;456:167, Cardiovasc Pathol 2019;43:107142)
  • Dual color chromogenic in situ hybridization (DISH or CISH): same interpretation as FISH with high concordance between the 2 methods; benefits include light microscopy (rather than fluorescent), ability to store slides, ability to evaluate morphology of counterstained tissues and lower cost and turnaround time (J Clin Lab Anal 2015;29:462, Cardiovasc Pathol 2019;43:107142)
Molecular / cytogenetics images

Contributed by Robin Elliott, M.D. and Kossivi Dantey, M.D.
MDM2 dual color ISH

MDM2 dual color ISH

MDM2 FISH in dedifferentiated liposarcoma

MDM2 FISH in dedifferentiated liposarcoma

Board review style question #1
MDM2 MDM2


A 72 year old man is found to have a large retroperitoneal tumor. Histology and chromogenic in situ hybridization for MDM2 are shown. What is the most likely diagnosis?

  1. Dedifferentiated liposarcoma
  2. Leiomyosarcoma
  3. Myxoid liposarcoma
  4. Pleomorphic liposarcoma
Board review style answer #1
A. Dedifferentiated liposarcoma

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