MYC protein expression is associated with poor prognosis in diffuse large B cell lymphoma patients treated with RCHOP chemotherapy

Zhou, Min; Wang, Jing; Ouyang, Jian; Xu, Jingyan; Chen, Bing; Zhang, Qiguo; Zhou, Rong-Fu; Yang, Yonggong; Shao, Xiaoyan; Xu, Yong; Chen, Ya‐Mei; Fan, Xiangshan; Wu, Hongyan

doi:10.1007/s13277-014-1907-z

Cited by 17 publications

(24 citation statements)

References 22 publications

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“…The main characteristics of the patients at diagnosis are listed in Table 1. The distribution of patients according to the biological marker-adjusted International Prognostic Index (B-IPI) [24, 25] (n = 49) was as follows: low risk, 2 cases (4%); low/intermediate risk, 18 cases (37%); high/intermediate risk, 12 cases (24%); and high risk, 17 cases (35%).…”

Section: Resultsmentioning

confidence: 99%

“…Currently, the International Prognostic Index is the most successful clinical model for predicting DLBCL outcome. Many efforts have been made to improve this model’s discriminatory capabilities [24–30]. Several prognostic models have been built for DLBCL.…”

Section: Discussionmentioning

confidence: 99%

“…An antibody against p65 (Beijing Zhongshan Golden Bridge Biotechnology Co. Ltd, dilution 1:100) was used in addition to an autostainer following the standard polymer method (Dako Autostainer Plus). MYC and BCL-2 staining was completed as we previously reported [24–26]. Immunohistochemistry was evaluated by 2 experienced hematopathologists using a multihead microscope.…”

Section: Methodsmentioning

confidence: 99%

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Prognostic value of expression of nuclear factor kappa-B/p65 in non-GCB DLBCL patients

et al. 2016

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PurposeWe estimated the expression of nuclear factor kappa B/p65 in non-germinal center B-cell-like subtype diffuse large B-cell lymphoma, to investigate its relationship to clinicopathological features, and to further evaluate its prognostic value and clarify its impact on survival.ResultsAmong the 49 patients enrolled in this study, 14 (28.6%) had positive p65 expression. The negative p65 group had significantly better survival compared to the positive p65 group in terms of both the 3-year estimated OS (91.2% vs. 39.3%, p = 0.003) and PFS (75.6% vs. 26.5%, p = 0.002). In patients with 4 or more risk factors, p65 was an independent prognostic factor of OS (HR 5.99, 95%CI=1.39-25.75, p=0.016) and PFS (HR 4.01, 95%CI=1.15-14.00, p=0.029).Materials and MethodsThe expression of the NF-κB/p65 protein was deteremined by immunohistochemistry in 49 non-GCB DLBCL. Survival was assessed by the Kaplan–Meier method and Cox multivariate analysis. The median patient follow-up period was 24 months.ConclusionsThe expression of NF-κB/p65 has prognostic value in high risk non-GCB DLBCL, and it is a suitable target for the development of new therapies.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Prognostic value of expression of nuclear factor kappa-B/p65 in non-GCB DLBCL patients

et al. 2016

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“…Recent reports have focused on MYC protein expression in aggressive B-cell lymphomas in an effort to identify poor prognostic subgroups. 8,9,16,[24][25][26][27][28][29][30] However, there is insufficient information regarding MYC protein expression and the correlation between MYC protein as measured by immunohistochemistry and MYC rearrangements in various subtypes of lymphomas. These considerations prompted our study, and the results show that the MYC protein is not uniformly expressed among or within a given subtype of lymphoma.…”

Section: Discussionmentioning

confidence: 99%

“…Some have used MYC protein staining in >40% of lymphoma cells, 8,9,16,26,28 whereas others have used >50% of lymphoma cells 10,27,30 to define MYC positivity. Moreover, different methods were used by different groups to establish these cutoff values.…”

Section: Discussionmentioning

confidence: 99%

Expression Profiles of MYC Protein and MYC Gene Rearrangement in Lymphomas

Chisholm

Bangs

Bacchi

et al. 2015

American Journal of Surgical Pathology

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MYC translocations are a defining feature of Burkitt lymphoma and a group of diffuse large B-cell lymphoma (DLBCL) with inferior outcome. However, the clinical relevance of MYC gene rearrangement and its relationship with MYC protein expression has not been well characterized in lymphomas. Tissue microarrays containing 1214 lymphomas were successfully evaluated by immunohistochemistry using anti-MYC clone Y69 and a dual-color break-apart fluorescence in situ hybridization probe to detect MYC gene rearrangements. Aggressive B-cell lymphomas including Burkitt lymphoma and DLBCL showed the highest level of MYC protein staining defined as staining in >50% of lymphoma cells. A significant proportion of plasmablastic, B-lymphoblastic and T-lymphoblastic, and extranodal NK/T-cell lymphomas also showed staining in >50% of cells, whereas only occasional plasma cell myeloma, mantle cell lymphoma, and classical Hodgkin lymphoma showed a high level of staining. Small B-cell lymphomas, when positive, showed MYC protein in <50% of cells. In aggressive B-cell lymphomas, MYC rearrangement and MYC immunohistochemistry showed a high concordance rate; however, some DLBCL and all T-cell and NK-cell lymphomas with MYC protein expression lacked MYC gene rearrangements. Our results provide a baseline for MYC protein expression in lymphomas and indicate that its expression is not specific to lymphoma subtypes, cell lineage, or expected clinical behavior and is highly variable. In addition, MYC protein expression is not necessarily correlated with MYC gene rearrangements and suggests the need for caution in the interpretation of MYC immunohistochemistry in the differential diagnosis of lymphomas.

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c‐MYC and p53 expression highlight starry‐sky pattern as a favourable prognostic feature in R‐CHOP‐treated diffuse large B‐cell lymphoma

Bouroumeau

Bussot

Bonnefoix

et al. 2021

The Journal of Pathology CR

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Diffuse large B‐cell lymphoma (DLBCL) is a clinically heterogeneous entity, in which the first‐line treatment currently consists of an immuno‐chemotherapy regimen (R‐CHOP). However, around 30% of patients will not respond or will relapse. Overexpression of c‐MYC or p53 is frequently found in DLBCL, but an association with prognosis remains controversial, as for other biomarkers previously linked with DLBCL aggressivity (CD5, CD23, or BCL2). The aim of this study was to explore the expression of these biomarkers and their correlation with outcome, clinical, or pathological features in a DLBCL cohort. Immunohistochemical (c‐MYC, p53, BCL2, CD5, and CD23), morphological (‘starry‐sky’ pattern [SSP]), targeted gene panel sequencing by next‐generation sequencing (NGS), and fluorescence in situ hybridisation analyses were performed on tissue microarray blocks for a retrospective cohort of 94 R‐CHOP‐treated de novo DLBCL. In univariate analyses, p53 overexpression (p53high) was associated with unfavourable outcome (p = 0.04) and with c‐MYC overexpression (p = 0.01), whereas c‐MYC overexpression was linked with an SSP (p = 0.004), but only tended towards an inferior prognosis (p = 0.06). Presence of a starry‐sky morphology was found to be correlated with better survival in p53high DLBCL (p = 0.03) and/or c‐MYC‐positive DLBCL (p = 0.002). Furthermore, NGS data revealed that these three variables were associated with somatic mutations (PIM1, TNFRSF14, FOXO1, and B2M) involved in B‐cell proliferation, survival, metabolism, and immune signalling. Taken together, these results show that the SSP pattern seems to be a protective factor in high‐risk DLBCL subgroups and highlight cell death as a built‐in failsafe mechanism to control tumour growth.

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MYC protein expression is associated with poor prognosis in diffuse large B cell lymphoma patients treated with RCHOP chemotherapy

Cited by 17 publications

References 22 publications

Prognostic value of expression of nuclear factor kappa-B/p65 in non-GCB DLBCL patients

Prognostic value of expression of nuclear factor kappa-B/p65 in non-GCB DLBCL patients

Expression Profiles of MYC Protein and MYC Gene Rearrangement in Lymphomas

c‐MYC and p53 expression highlight starry‐sky pattern as a favourable prognostic feature in R‐CHOP‐treated diffuse large B‐cell lymphoma

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