Fluorescent nanoparticle‐mediated semiquantitative MYC protein expression analysis in morphologically diffuse large B‐cell lymphoma

Purpose Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis. Patients and Methods We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation. Results In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations. Conclusion Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.

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C-MYC Protein Expression and High Ki-67 Proliferative Index are Predictives of Disease Relapse in Diffuse Large B Cell Lymphoma

Asian Pacific Journal of Cancer Biology ◽

10.31557/apjcb.2021.6.1.15-20 ◽

2021 ◽

Vol 6 (1) ◽

pp. 15-20

Author(s):

Mahmoud Tag El-Hussien ◽

Nadia Mokhtar ◽

Eman Naguib Khorshed

Keyword(s):

Protein Expression ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Statistical Prediction ◽

Proliferative Index ◽

Ki 67 ◽

Large B Cell Lymphoma ◽

Large B Cell

Objective: To evaluate the status of C-MYC protein expression and Ki-67 proliferative index and to clarify their role in predicting relapse of diffuse large B cell lymphoma (DLBL). Materials and Methods: A retrospective study conducted on 50 cases diagnosed as DLBL in a 3 years’ time period from January 2014 till December 2016, collected from the archive of Pathology Departments of the National Cancer Institute Cairo - Egypt, Misr University for Science and Technology and private labs of authors. The diagnosis of DLBL for all cases, both nodal and extranodal, was confirmed by histopathologic examination and immunophenotyping. Automated immunohistochemical staining using antibodies against C-MYC protein and MIB-1 was used to evaluate the C-MYC expression in tumor cells and to assess their proliferative ability by calculating Ki-67 labelling index. The relation between the percentage of C-MYC protein expression, Ki-67 proliferative index, clinical data and the relapse status during the follow up period were analyzed. Results: A total of 50 cases of DLBL in both nodal and extra-nodal sites were included. Twenty-three cases (46%) were expressing the C-MYC protein, and 29 cases (58%) showed high Ki-67 proliferative index. Twenty-two cases (44%) relapsed during the follow-up period. Positive C-MYC protein expression was significantly associated with high Ki-67 proliferative index. C-MYC protein expression and high Ki-67 proliferative index were independently associated with disease relapses in 81.8% and 86.4% of cases respectively. Cases with combined C-MYC protein expression and high Ki-67 proliferative index showed statistical prediction of relapse in 81.8% of cases. Conclusion: C-MYC protein expression and high Ki-67 proliferative index were independently associated with relapse of diffuse large B cell lymphoma. Furthermore, the combined positive C-MYC protein expression and high Ki-67 proliferative index is better than a single positive test in predicting relapses among DLBL patients.

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Value of PD-L1 Protein Expression in the Combined Prognostic Model of Diffuse Large B-Cell Lymphoma

Clinical oncohematology ◽

10.21320/2500-2139-2021-14-3-308-314 ◽

2021 ◽

Vol 14 (3) ◽

pp. 308-314

Author(s):

Svetlana Valerevna Samarina ◽

N.Yu. Semenova ◽

N.V. Minaeva ◽

D.A. Dyakonov ◽

V.A. Rosin ◽

...

Keyword(s):

Protein Expression ◽

B Cell ◽

Prognostic Model ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

L1 Protein ◽

Large B Cell

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Low rather than high Ki-67 protein expression is an adverse prognostic factor in diffuse large B-cell lymphoma

Leukemia & Lymphoma ◽

10.1080/10428190802140055 ◽

2008 ◽

Vol 49 (8) ◽

pp. 1501-1509 ◽

Cited By ~ 21

Author(s):

Sverker Hasselblom ◽

Börje Ridell ◽

Margret Sigurdardottir ◽

Ulrika Hansson ◽

Herman Nilsson-Ehle ◽

...

Keyword(s):

Prognostic Factor ◽

Protein Expression ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Ki 67 ◽

Adverse Prognostic Factor ◽

Large B Cell Lymphoma ◽

Large B Cell

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A 70% cut-off for MYC protein expression in diffuse large B cell lymphoma identifies a high-risk group of patients

Haematologica ◽

10.3324/haematol.2019.235556 ◽

2020 ◽

Vol 105 (11) ◽

pp. 2667-2670 ◽

Cited By ~ 3

Author(s):

Marita Ziepert ◽

Stefano Lazzi ◽

Raffaella Santi ◽

Federica Vergoni ◽

Massimo Granai ◽

...

Keyword(s):

High Risk ◽

Protein Expression ◽

B Cell ◽

Cell Lymphoma ◽

Risk Group ◽

B Cell Lymphoma ◽

High Risk Group ◽

Large B Cell Lymphoma ◽

Large B Cell

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Effect of siRNA interference of ubiquitin-specific protease 9X on apoptosis and growth of diffuse large B cell lymphoma cell line

Materials Express ◽

10.1166/mex.2020.1653 ◽

2020 ◽

Vol 10 (3) ◽

pp. 446-453

Author(s):

Wei Peng ◽

Meizuo Zhong ◽

Youhong Tang

Keyword(s):

B Cells ◽

Protein Expression ◽

B Cell ◽

Cell Apoptosis ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Specific Protease ◽

Sirna Interference ◽

Large B Cell

Ubiquitin-specific protease 9X (USP9X) is crucial in the diagnosis and treatment of many tumor types, but its role in Diffuse Large B Cell Lymphoma (DLBCL) has not been determined. The current study aimed to examine the effects of RNA interference on USP9X expression, and subsequently on the bioactivity of DLBCL Farage and Pfeiffer cells. There were two groups in the study: USP9X-siRNA and NC. USP9X siRNA was transiently transferred into DLBCL cells by Cationic liposome. The total RNA was extracted using Fe2O3 and was retrieved into the DNA using the MagBeads Total RNA Extraction Kit. The protein expression of USP9X in Farage, Pfeiffer, and normal human B cell line at the cellular level was observed by Western blot. The Farage and Pfeiffer cells were infected with USP9X-siRNA. Cell apoptosis and cell growth viability were analyzed by flow cytometry and CCK8, Mcl-1 protein, a potential target of USP9X, and apoptosis factor proteins (such as Bak, Cytochrome C, Caspase 3, Caspase 8, PARP) were detected by Western blot after siRNA interference. The results showed that the protein expression of USP9X in malignant B cells was four times higher than that of the normal B cells. Inhibition of USP9X reduced the Mcl-1 activity, and increased the caspase-3, Bak and Cytochrome C activity. In the malignant B cells, Mcl-1 and Bak were binding in vivo; Bak was a new partner of Mcl-1. Inhibition of USP9X reduced cell proliferation and increased apoptosis. The expression of USP9X is upregulated in Diffuse large B cell lymphoma cells, Farage, and Pfeiffer. Inhibition expression of USP9X may induce cell apoptosis, inhibit cell growth, and downregulate Mcl-1 protein expression in Diffuse large B cell lymphoma cells, Farage, and Pfeiffer. USP9X has the ability in regulating cell apoptosis.

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Hypoxia-Inducible Factor-1 α Expression Predicts Superior Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP

Journal of Clinical Oncology ◽

10.1200/jco.2009.24.1893 ◽

2010 ◽

Vol 28 (6) ◽

pp. 1017-1024 ◽

Cited By ~ 39

Author(s):

Andrew M. Evens ◽

Laurie H. Sehn ◽

Pedro Farinha ◽

Beverly P. Nelson ◽

Adekunle Raji ◽

...

Keyword(s):

Protein Expression ◽

B Cell ◽

Germinal Center ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Hypoxia Inducible Factor ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Wide Range ◽

Large B Cell

Purpose Hypoxia-inducible factor (HIF) controls the expression of genes in response to hypoxia, as well as a wide range of other cellular processes. We previously showed constitutive stabilization of HIF-1α in the majority of patients with diffuse large B-cell lymphoma (DLBCL). To our knowledge, the prognostic significance of HIF in lymphoma has never been investigated. Patients and Methods We studied the immunohistochemical protein expression of HIF-1α on tissue microarrays from 153 patients with DLBCL treated in sequential cohorts with cyclophosphamide, doxorubicin, oncovin, and prednisone (CHOP) or rituximab-CHOP (R-CHOP) from 1999 to 2002. Results were correlated with patient outcome. Results Median follow-up for all patients was 80 months. Among all patients, HIF-1α was expressed in 62% of germinal center and 59% of non–germinal center patients. With HIF-1α analyzed as a dependent variable, there were no survival differences in CHOP-treated patients. In the R-CHOP group, however, HIF-1α protein expression correlated with significantly improved progression-free survival (PFS) and overall survival (OS). Five-year PFS for HIF-1α–positive patients was 71% v 43% for HIF-1α–negative patients (P = .0187), whereas 5-year OS was 75% and 54%, respectively (P = .025). In multivariate analysis with International Prognostic Index criteria, HIF-1α remained a significant predictor for PFS (P = .026) and OS (P = .043). Compared with other biomarkers, HIF-1α correlated only with BCL6 (P = .004). In terms of gene expression, we found several common gene associations of HIF-1α and the stromal-1 signature with genes predominantly involved in regulation of the extracellular matrix (eg, BGN, COL1A2, COL5A1, and PLOD2). Conclusion The expression of HIF-1α protein is an important independent favorable prognostic factor for survival in patients with DLBCL treated with R-CHOP.

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