Loss of RUNX3 expression is an independent adverse prognostic factor in diffuse large B-cell lymphoma

Abstract

Runt-related transcription factor-3 (RUNX3) is an apoptotic factor correlated with tumorigenesis and cancer progression. Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been shown to mediate silencing of RUNX3. We investigated RUNX3 and EZH2 expression in diffuse large B-cell lymphoma (DLBCL). A chart review was conducted and tissue-microarray (TMA) was constructed using archived tissue from 83 DLBCL cases. RUNX3 and EZH2 protein expression was correlated with immunophenotypic subtypes and survival. Loss of RUNX3 was observed in 20 cases; EZH2 expression was observed in 59 cases. RUNX3-negative tumors had significantly lower overall and recurrence-free survival (log-rank test, p < 0.0001 for each). No correlation was found between RUNX3 and EZH2 staining (r = 0.14; p = 0.2). Results suggest a role for the RUNX3 gene in the pathogenesis of DLBCL. Loss of RUNX3 expression strongly correlated with adverse prognosis, independent of subtype. Further studies are warranted to elucidate the biology and prognostic utility of RUNX3 in DLBCL.

Biomarkers and novel therapeutic approaches for diffuse large B-cell lymphoma in the era of precision medicine

“…Tissue microarray-based FISH has been utilized in DLBCL to assess the role of BCL-6 rearrangement on the outcome for patients treated with CHOP or R-CHOP [47]. Expression of other genes, including PATZ1, MYC-3, and RUNX3, as well as microRNAs and non-coding RNAs, have also been assessed for their prognostic and diagnostic utility in DLBCL [48][49][50][51]. Comparative arrays of genomic hybridisation and single nucleotide polymorphism (SNP) arrays are often used to distinguish between DLBCL subtypes [52].…”

New developments in the pathology of malignant lymphoma: a review of the literature published from June–August 2016

“…Duncan et al [ 29 ] take a more traditional approach by analyzing protein expression of Runt-related transcription factor-3 (RUNX3) and enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, which has been shown to mediate silencing of RUNX3. They found in 83 DLBCL cases loss of RUNX3 in 20 cases; EZH2 expression was observed in 59 cases.…”

Prognostic Value of Histone Modifying Enzyme EZH2 in RCHOP-Treated Diffuse Large B-Cell Lymphoma and High Grade B-Cell Lymphoma

“…Despite the well-established mutational status and driver function of this gene in DLBCL, the prognostic value of its mutational status remains controversial, with the few published data mostly pointing towards a lack thereof [7,11]. In spite of this, analysis of publicly available data from patients included in two different studies [5]-warranting cautious interpretation, given the potential use of different inclusion and outcome criteriaassociates EZH2 mutated DLBCL with worse Overall and Progression Free Survival, albeit not significantly (Figure A1) Furthermore, when considering EZH2 expression, some studies suggest that it may be a promising biomarker in DLBCL [12][13][14][15][16][17][18][19]. Nonetheless, published data are inconsistent, possibly due to the use of different methodologies (universally semiquantitative), different positivity threshold, inclusion of heterogeneously treated patients and small number of patients per study (median number of patients per study: 68, interquartile range: 37 to 92).…”