EZH2 expression is associated with inferior overall survival in mantle cell lymphoma

Martínez-Baquero, Diana Lucía; Sakhdari, Ali; Mo, Huan; Kim, Dowhan; Kanagal‐Shamanna, Rashmi; Li, Shaoying; Young, Ken H.; O’Malley, Dennis P.; Doğan, Ahmet; Jain, Preetesh; Wang, Michael L.; McDonnell, Timothy J.; Miranda, Roberto N.; Vega, Francisco; Medeiros, L. Jeffrey; Ok, Chi Young

doi:10.1038/s41379-021-00885-9

Cited by 8 publications

(6 citation statements)

References 48 publications

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“…Early evidence comes from solid tumor studies where EZH2 overexpression has been observed in multiple cancers, including prostate cancer, breast cancer, bladder cancer, endometrial cancer, and melanoma [2]. More recently, we and other groups found EZH2 overexpression in a range of hematologic malignancies including B-cell lymphomas, Hodgkin lymphomas, histiocytic and dendritic cell neoplasms, subsets of T-cell neoplasms, plasma cell neoplasms, and myeloid neoplasms [3][4][5][6][7][8][9]. Targeting EZH2 has emerged as a new therapeutic approach against the epigenetic mechanisms of carcinogenesis in recent years.…”

Section: Introductionmentioning

confidence: 84%

Upregulation of Enhancer of Zeste Homolog 2 (EZH2) with Associated pERK Co-Expression and PRC2 Complex Protein SUZ12 Correlation in Adult T-Cell Leukemia/Lymphoma

Chai,

Choudhuri,

Gong

et al. 2024

Cancers

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EZH2, a subunit of the polycomb repressive complex 2 (PRC2), is an important methyltransferase that catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3). EZH2 is overexpressed in various malignancies. Here, we investigated EZH2 expression and potential signaling molecules that correlate with EZH2 expression in ATLL and other T-cell neoplasms. Immunohistochemical staining (IHC) was performed for EZH2, pERK, MYC, and pSTAT3 on 43 ATLL cases and 104 cases of other T-cell neoplasms. Further IHC studies were conducted for Ki-67, SUZ12, and H3K27me3 on ATLL cases. All ATLL cases showed EZH2 overexpression. In other T-cell neoplasms, a high prevalence of EZH2 overexpression was identified (86%), except for T-PLL (33%). In ATLL, EZH2 overexpression correlated with pERK co-expression (86%), while only a small subset of cases showed MYC (7%) or pSTAT3 (14%) co-expression. In the other T-cell neoplasms, there was a variable, but higher, co-expression of EZH2 with pERK, MYC, and pSTAT3. In ATLL, enhanced EZH2 expression correlated with higher Ki-67 staining, SUZ12 (another PRC2 subunit), and H3K27me3 co-expression. In conclusion, EZH2 is overexpressed in ATLL and is associated with pERK expression. It correlates with an increased proliferation index, indicating an aggressive clinical course. EZH2 also correlates with SUZ12 and H3K27me3 co-expression, suggesting its PRC2-dependent catalytic activity through trimethylation. Additionally, EZH2 is overexpressed in most T-cell neoplasms, suggesting that EZH2 could function as an oncogenic protein in T-cell tumorigenesis. EZH2 and pERK could serve as potential therapeutic targets for treating aggressive ATLL. EZH2 could also be targeted in other T-cell neoplasms.

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Section: Introductionmentioning

confidence: 84%

Upregulation of Enhancer of Zeste Homolog 2 (EZH2) with Associated pERK Co-Expression and PRC2 Complex Protein SUZ12 Correlation in Adult T-Cell Leukemia/Lymphoma

Chai,

Choudhuri,

Gong

et al. 2024

Cancers

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“…In breast cancer, although high EZH2 and low H3K27me3 correlate with poor prognosis of estrogen receptor-positive (ER+) breast cancers, the methyltransferase EZH2 is not required for mammary cancer development ( Bae et al, 2015 ). In mantle cell lymphoma, EZH2 expression is associated with inferior OS and EZH2 expression shows a weak correlation with other PRC2 complex molecules, but no correlation with H3K27me3 expression, or loss of major histocompatibility complex (MHC) I/II ( Martinez-Baquero et al, 2021 ). In contrast, our findings are consistent with the study of mantle cell lymphoma, that there is no correlation between the two markers.…”

Section: Discussionmentioning

confidence: 99%

Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma

et al. 2022

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BackgroundEnhancer of zeste homolog 2 (EZH2), an important epigenetic regulator, that mainly regulates histone H3 lysine 27 trimethylation (H3K27me3) through histone methyltransferase, and participates in promoting the development of tumors. At present, the loss of H3K27me3 expression in meningioma is a poor prognostic factor, but the research of EZH2 in meningioma is rare. Therefore, we aim to explore the expression of EZH2 in the meningioma and its correlation with the prognosis and immune microenvironment and lay the foundation for the subsequently potential targeted therapy and immunotherapy for meningioma.MethodsTissue microarray immunohistochemistry staining was performed on 276 meningioma samples from Sun Yat-sen University Cancer Center. Expression levels of EZH2, H3K27me3, Ki67, programmed cell death protein 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), CD4, CD8, CD20, FOXP3, CD68, and CD163 were evaluated. Cox regression analyses were performed, and the Kaplan–Meier (KM) method was used to construct survival curves. In addition, we use biological information methods to analyze the mRNA expression of EZH2 and its relationship with the prognosis and immune microenvironment in the gene expression omnibus (GEO) database.ResultsEnhancer of zeste homolog 2 expression is concentrated in World Health Organization (WHO) grades 2 and 3 meningiomas (8.3+ and 33.3%+). We found that EZH2 expression was associated with a worse prognosis in meningioma (P < 0.001), the same results were confirmed in the GEO database (P < 0.001). Both EZH2 expression and H3K27me3 deletion (P = 0.035) predicted a worse prognosis, but EZH2 has no correlation with H3K27me3 expression. EZH2 expression was closely associated with increased Ki67 index (P < 0.001). In addition, EZH2 was associated with the immune microenvironment and positively correlated with PD-L1 expression (P < 0.001).ConclusionEnhancer of zeste homolog 2 is a new prognostic biomarker in meningioma. It correlates with PD-L1 expression and closely related to tumor immunosuppression. Our research can provide a reference for the potential targeted therapy and immunotherapy of meningioma in the future.

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“…Gene expression profiling was performed using RNA derived from FFPE tissue and by using the nCounter PanCancer Pathway Panel (NanoString Technologies) as described previously. 16 The data quality control and normalization were performed on nSolver Analysis Software 4.0 (NanoString Technologies) with the default setting. Flagged specimens were removed from subsequent analysis.…”

Section: Gene Expression Profilingmentioning

confidence: 99%

Blastoid and Pleomorphic Mantle Cell Lymphoma Demonstrate Distinct Clinicopathologic and Genetic Features

Khanlari¹,

Mo²,

Kim³

et al. 2023

American Journal of Surgical Pathology

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The blastoid (B) and pleomorphic (P) variants of mantle cell lymphoma (MCL) are associated with aggressive clinical behavior. In this study, we collected 102 cases of B-MCL and P-MCL from untreated patients. We reviewed clinical data, analyzed morphologic features using an image analysis tool (ImageJ) and we assessed mutational and gene expression profiles. The chromatin pattern of lymphoma cells was assessed quantitatively by the pixel value. Cases of B-MCL showed a greater median pixel value with lower variation compared with P-MCL, indicating a homogeneously euchromatin-rich pattern in B-MCL. In addition, the Feret diameter of the nuclei was significantly smaller (median 6.92 vs. 8.49 µm per nucleus, P<0.001) and had a lesser degree of variation in B-MCL compared with P-MCL, indicating that B-MCL cells have smaller cells with a more monomorphic appearance. B-MCL showed a significantly higher median Ki-67 proliferation rate (60% vs. 40%, P=0.003), and affected patients had poorer overall survival compared with those with P-MCL (median overall survival: 3.1 vs. 8.8 y, respectively, P=0.038). NOTCH1 mutation was significantly more frequent in B-MCL compared with P-MCL (33% and 0%, respectively, P=0.004). Gene expression profiling showed 14 genes overexpressed in B-MCL cases and gene set enrichment assay for the overexpressed genes showed significant enrichment in the cell cycle and mitotic transition pathways. We also report a subset of MCL cases that has blastoid chromatin but a higher degree of pleomorphism in nuclear size and shape, designated here as hybrid MCL. Hybrid MCL cases had a similar Ki-67 proliferation rate, mutation profile, and clinical outcome to B-MCL and distinct from P-MCL. In summary, these data suggest biological differences between B-MCL and P-MCL cases justifying their separate designation when possible.

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EZH2 expression is associated with inferior overall survival in mantle cell lymphoma

Cited by 8 publications

References 48 publications

Upregulation of Enhancer of Zeste Homolog 2 (EZH2) with Associated pERK Co-Expression and PRC2 Complex Protein SUZ12 Correlation in Adult T-Cell Leukemia/Lymphoma

Upregulation of Enhancer of Zeste Homolog 2 (EZH2) with Associated pERK Co-Expression and PRC2 Complex Protein SUZ12 Correlation in Adult T-Cell Leukemia/Lymphoma

Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma

Blastoid and Pleomorphic Mantle Cell Lymphoma Demonstrate Distinct Clinicopathologic and Genetic Features

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