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Prognostic Value of Histone Modifying Enzyme EZH2 in RCHOP-Treated Diffuse Large B-Cell Lymphoma and High Grade
Sara Petronilho1,2, José Pedro Sequeira2, Sofia Paulino1,2
1Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200072 Porto, Portugal.
Insights
EZH2 immunoexpression did not predict outcomes in Diffuse Large B-cell Lymphoma (DLBCL) or High-Grade B-cell Lymphoma (HGBCL) patients treated with RCHOP. However, EZH2 and BCL2 co-expression indicated a worse prognosis.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Diffuse Large B-cell Lymphoma (DLBCL) is aggressive and heterogeneous, with High-Grade B-cell Lymphomas (HGBCL) now recognized as a distinct entity with poorer prognosis.
- While RCHOP therapy is effective, approximately one-third of patients either do not respond or relapse.
- Alterations in histone modifying enzymes, including EZH2, are common in DLBCL, but their prognostic significance remains debated.
Purpose of the Study:
- To investigate the prognostic value of EZH2 immunoexpression in DLBCL and HGBCL patients undergoing RCHOP treatment.
- To explore the association between EZH2 expression and patient outcomes in these aggressive lymphoma subtypes.
Main Methods:
- A retrospective cohort study was conducted on 125 patients diagnosed with DLBCL or HGBCL and treated with RCHOP.
- EZH2 immunoexpression levels were assessed and correlated with clinical outcomes.
- Subgroup analyses, including Germinal Center (GC) versus non-GC DLBCL, were performed.
Main Results:
- EZH2 expression levels were comparable between DLBCL and HGBCL diagnostic groups, as well as between DLBCL-NOS molecular subgroups (GC vs. non-GC).
- No significant association was found between EZH2 expression levels and patient outcomes, including event-free and overall survival.
- Notably, EZH2 and BCL2 co-expression was significantly linked to worse event-free survival and overall survival.
Conclusions:
- Despite EZH2 mutations being more prevalent in GC-DLBCL, similar EZH2 expression levels in DLBCL-NOS groups suggest non-mutational deregulation mechanisms.
- The findings imply that EZH2 antagonists could potentially benefit non-GC DLBCL patients.
- EZH2/BCL2 co-expression serves as a significant adverse prognostic marker in RCHOP-treated DLBCL and HGBCL.
Background:
DLBCL represent a heterogeneous group of aggressive diseases. High grade B-cell lymphomas (HGBCL) were recently individualized from DLBCL as a discrete diagnostic entity due to their worse prognosis. Currently, although most patients are successfully treated with RCHOP regimens, 1/3 will either not respond or ultimately relapse. Alterations in histone modifying enzymes have emerged as the most common alterations in DLBCL, but their role as prognostic biomarkers is controversial. We aimed to ascertain the prognostic value of EZH2 immunoexpression in RCHOP-treated DLBCL and HGBCL.
Results:
We performed a retrospective cohort study including 125 patients with RCHOP-treated DLBCL or HGBCL. EZH2 expression levels did not differ between diagnostic groups or between DLBCL-NOS molecular groups. We found no associations between EZH2 expression levels and outcome, including in the subgroup analysis (GC versus non-GC). Nonetheless, EZH2/BCL2 co-expression was significantly associated with worse outcome (event free survival and overall survival).
Conclusion:
Although EZH2 mutations are almost exclusively found in GC-DLBCL, we found similar EZH2 expression levels in both DLBCL-NOS molecular groups, suggesting non-mutational mechanisms of EZH2 deregulation. These findings suggest that the use of EZH2 antagonists might be extended to non-GC DLBCL patients with clinical benefit. EZH2/BCL2 co-expression was associated with a worse outcome.
