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TP53 mutation is frequent in mantle cell lymphoma with EZH2 expression and have dismal outcome when both are present

  • 0Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Human Pathology +

|

March 9, 2024

|

March 9, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Enhancer of zeste homolog 2 (EZH2) expression in mantle cell lymphoma (MCL) correlates with TP53 mutations and aggressive disease features. Combined EZH2 expression or TP53 mutation indicates poor prognosis, with dismal outcomes when both are present.

Area Of Science

  • Oncology
  • Hematology
  • Molecular Biology

Background

  • Enhancer of zeste homolog 2 (EZH2) is expressed in approximately 40% of mantle cell lymphoma (MCL) cases.
  • EZH2 expression is linked to aggressive histology, high proliferation rates (Ki-67), p53 abnormalities, and reduced overall survival (OS).

Purpose Of The Study

  • To investigate the molecular landscape of EZH2-expressing MCL (EZH2+ MCL) using a targeted gene panel.
  • To explore the relationship between EZH2 expression, TP53 mutations, and clinical-pathological features in MCL.

Main Methods

  • Utilized an 11-gene next-generation sequencing panel (including ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2, UBR5).
  • Performed immunohistochemistry to assess p53 mutant patterns.
  • Correlated molecular findings with clinical data, including histology and Ki-67 proliferation index.

Main Results

  • EZH2+ MCL exhibited a higher frequency of TP53 mutations compared to EZH2-negative MCL (41.2% vs. 19.1%, p=0.045).
  • Overlapping features between TP53 mutation and EZH2 expression included aggressive histology, high Ki-67, and p53 mutant patterns.
  • EZH2 expression correlated with high Ki-67 irrespective of TP53 mutation status.
  • Aggressive histology was associated with either EZH2 expression or TP53 mutation, potentially through independent pathways.

Conclusions

  • TP53 mutations are more common in EZH2-expressing MCL and contribute to the p53 mutant phenotype.
  • Both EZH2 expression and TP53 mutation are independently associated with aggressive disease and inferior outcomes in MCL.
  • The co-occurrence of EZH2 expression and TP53 mutation signifies a particularly dismal prognosis for MCL patients.

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