Diagnostic Accuracy of Immunohistochemical Expression of p16, MDM2, and CDK4 in Well-Differentiated and De-Differentiated Liposarcoma in MDM2 Fluorescent <em>in situ </em>Hybridisation Confirmed Cases

J Coll Physicians Surg Pak. 2024 Sep;34(9):1051-1055. doi: 10.29271/jcpsp.2024.09.1051.

Abstract

Objective: To establish the diagnostic utility of immunohistochemistry markers p16 along with MDM2 and CDK-4 in confirming the diagnosis of well-differentiated and de-differentiated liposarcoma while taking Fluorescent in situ Hybridisation (FISH) as a gold standard.

Study design: A cross-sectional study. Place and Duration of the Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from 30th January 2022 to 30th June 2023.

Methodology: A standard panel of three immunohistochemistry markers p16, MDM2, and CDK4 were applied to 36 cases of atypical lipomatous tumours, well-differentiated liposarcoma (WDLPS), and de-differentiated liposarcoma (DDLPS), on which the gold standard FISH was already performed. The sample size was calculated with the help of a WHO calculator taking prevalence 1-2% in Pakistani population. Qualitative variables such as gender and site of tumour were presented by calculating frequency and percentages and comparison of Immunohistochemistry results with FISH was done by using a 2x2 table.

Results: The sensitivity and specificity of this triple marker panel for detecting WDLPS/DDLPS were 43.47% and 15.38%, respectively. The sensitivity and specificity of CDK4 for detecting WDLPS / DDLPS were 82.6% and 15.4%, those of MDM2 were 73.9% and 61.5 %, and those of p16 were 60.9% and 53.8%, respectively.

Conclusion: Among all three markers, CDK4 was the most sensitive and MDM2 was the most specific marker for detecting WDLPS-DDLPS. It also showed that a combination of these three markers improves the diagnostic credibility of the immunohistochemistry in diagnosing DDLPS and WDLPS but FISH is the most reliable and confirmatory method.

Key words: De-differentiated liposarcoma, Well-differentiated liposarcoma, P16, CDK4, MDM2.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / metabolism
  • Cross-Sectional Studies
  • Cyclin-Dependent Kinase 4* / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16* / metabolism
  • Female
  • Humans
  • Immunohistochemistry*
  • In Situ Hybridization, Fluorescence*
  • Liposarcoma* / diagnosis
  • Liposarcoma* / metabolism
  • Liposarcoma* / pathology
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-mdm2* / metabolism
  • Sensitivity and Specificity

Substances

  • Proto-Oncogene Proteins c-mdm2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase Inhibitor p16
  • MDM2 protein, human
  • CDK4 protein, human
  • Biomarkers, Tumor
  • CDKN2A protein, human