Comparison of Chromogenic In Situ Hybridization and Fluorescence In Situ Hybridization for the Evaluation of MDM2 Amplification in Adipocytic Tumors

J Clin Lab Anal. 2015 Nov;29(6):462-8. doi: 10.1002/jcla.21794. Epub 2014 Aug 17.

Abstract

Background: Atypical lipomatous tumor/well-differentiated liposarcoma (ALT-WDLPS) and dedifferentiated liposarcoma (DDLPS) are characterized cytogenetically by a 12q13-15 amplification involving the mouse double minute 2 (MDM2) oncogene. Fluorescence in situ hybridization (FISH) is used frequently to detect this amplification and aid with the diagnosis of these entities, which is difficult by morphology alone. Recently, bright-field in situ hybridization techniques such as chromogenic in situ hybridization (CISH) have been introduced for the determination of MDM2 amplification status.

Methods: The present study compared the results of FISH and CISH for detecting MDM2 amplification in 41 cases of adipocytic tumors. Amplification was defined in both techniques as a MDM2/CEN12 ratio of 2 or greater.

Results: Eleven cases showed amplification with both FISH and CISH, and 26 cases showed no amplification with both methods. Two cases had discordant results between CISH and FISH, and two cases were not interpretable by CISH.

Conclusion: CISH is advantageous for allowing pathologists to evaluate the histologic and molecular alterations occurring simultaneously in a specimen. Moreover, CISH is found to be more cost- and time-efficient when used with automation, and the signals do not quench over time. CISH technique is a reliable alternative to FISH in the evaluation of adipocytic tumors for MDM2 amplification.

Keywords: MDM2 protein; adipose tissue; human gene amplification in situ hybridization chromogenic compounds; neoplasms.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Gene Amplification*
  • Humans
  • In Situ Hybridization / classification*
  • In Situ Hybridization / methods*
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Soft Tissue Neoplasms / genetics*
  • Soft Tissue Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2