EZH2 expression is dependent on MYC and TP53 regulation in diffuse large B‐cell lymphoma

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2020-04, Vol.128 (4), p.308-315
• Main Authors: Neves Filho, Eduardo Henrique, Hirth, Carlos Gustavo, Frederico, Igor Allen, Burbano, Rommel Mario, Carneiro, Thiago, Rabenhorst, Silvia Helena
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; B-cell lymphoma; Bcl-6 protein; Biomarkers, Tumor - genetics; Cell Proliferation - genetics; Chromosome rearrangements; Diffuse large B‐cell lymphoma; Enhancer of Zeste Homolog 2 Protein - genetics; EZH2; Female; Gene Expression Regulation, Neoplastic - genetics; Germinal Center - physiology; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse - genetics; Male; Middle Aged; MYC; Myc protein; p53 Protein; Pathogenesis; Proto-Oncogene Proteins c-myc - genetics; R‐CHOP; TP53; Translocation; Translocation, Genetic - genetics; Tumor Suppressor Protein p53 - genetics; Tumors; Up-Regulation - genetics; Young Adult
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/apm.13029

EZH2 is an important epigenetic regulator, but its role in diffuse large B‐cell lymphoma (DLBCL) pathogenesis and its relationship with MYC, BCL2, and TP53 expression, chromosomal rearrangements, and clinical features are still poorly understood. So, we investigated EZH2 expression and its associations with the immunophenotypic presentations, including MYC, BCL2, and TP53 expression, MYC, BCL2, and BCL6 translocation status, clinicopathological features, and therapeutic response to R‐CHOP in a series of 139 DLBCL cases. EZH2 positivity was associated with MYC and TP53 expression (p = 0.0002 and p = 0.0000, respectively) and to high proliferative index (Ki67>70%, p = 0.0082). No associations were found among EZH2 expression and chromosomal translocation status. The non‐germinal center (nGC) DLBCL presented most of associations observed in the general sample; however, only TP53 immunodetection showed associations with EZH2 expression in the germinal center (GC) DLBCL. EZH2 expression had no impact on therapeutic efficacy in R‐CHOP‐treated patients. In conclusion, EZH2 seems to be upregulated by MYC, to rely on TP53 alterations, and is associated with high proliferative tumors in DLBCL, which might be dependent on GC or nGC subclassifications. Furthermore, it is not a therapeutic efficacy marker to R‐CHOP in our series.