Predictive Value of Bcl-2 and Bcl-6 Protein Expression in Diffuse Large B-Cell Lymphoma Patients from a Single Institution.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4546-4546
Author(s):  
Ewa Paszkiewicz-Kozik ◽  
Olga Mioduszewska ◽  
Irena Federowicz ◽  
Ewa Kraszewska ◽  
Elzbieta Kulczycka ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Predictive Value ◽  
Death Rate ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
B Cell Lymphoma ◽  
Advanced Clinical Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Bcl-2 and Bcl-6 protein expression has been reported to predict progression-free (PFS) and overall (OS) survival of patients with Diffuse Large B-cell Lymphoma (DLBCL) in retrospective and prospective clinical studies. Reports on Bcl-2 expression frequency and predictive value have been conflicting. In the current study, paraffin-embedded tissue specimens from 79 newly diagnosed DLBCL patients subsequently treated with CHOP-like chemotherapy without rituximab were studied retrospectively using immunohistochemistry to evaluate expected influence of Bcl-2 and Bcl-6 on clinical outcome. Bcl-2 and Bcl-6 positivity was defined as staining in any of lymphoma cells and it was demonstrated in 78% of Bcl-2 and 58% of Bcl-6 patients. Frequency of Bcl-2 protein expression in our study was much higher then reported by others. Combinations of possible positive/negative staining results: Bcl2+/Bcl6+, Bcl-2+/Bcl-6-, Bcl-2-/Bcl-6+, Bcl-2-/Bcl-6- were found in 46%, 33%, 13%, and 9% of cases, respectively. Complete remission (CR) after initial chemotherapy was achieved in 54 of 74 evaluable patients (73%) and 6 patients (8%) had progressive disease (PD). CR rate was higher and relapse and death rate was lower in patients with Bcl-6+ tumor irrespective of Bcl-2 status. In patients with Bcl-6 negative lymphoma CR rate was higher when Bcl-2 was positive, but relapse and death rate was not affected by Bcl-2. Median OS and PFS were not reached after 21.3 months of follow-up in this group of patients. In the analysis using multivariate proportional hazards regression model, advanced clinical stage (CS III and IV vs. CS I and II) was the only significant factor predicting OS (p<0.002). Risk of relapse or PD was significantly lower in patients with IPI score of 0 or 1 vs. > 1 (p<0.001), and in patients with both Bcl-2 and Bcl-6 positive lymphoma (p=0.04) as compared to patients with all other protein expression combinations. When analyzed separately, Bcl-6 positivity alone predicted PFS (p=0.025) while Bcl-2 was not significant (p=0.98). These results support predictive value of Bcl-6 protein expression for response to CHOP and PFS in DLBCL patients and are in agreement with the recent findings from the E4494 trial group (Blood102:101a, Abstr. 345, 2003). Unlike the findings of the GELA study (Blood101: 4279, 2003), our data fail to confirm predictive role of Bcl-2 protein. Figure Figure

scholarly journals High Rates of HTLV-1 Seropositivity in Patients with EBV-Positive Diffuse Large B-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5049-5049
Author(s):  
Brady E Beltran ◽  
Domingo Morales ◽  
Pilar Quinones ◽  
Jose M Malaga ◽  
Jorge J Castillo
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Early Stage ◽  
Clinical Stage ◽  
B Cell Lymphoma ◽  
Advanced Clinical Stage ◽  
Large B Cell Lymphoma ◽  
High Prevalence ◽  
Large B Cell

Abstract Background: Epstein-Barr virus (EBV)-positive diffuse large B cell lymphoma (DLBCL) of the elderly is a novel entity included in the most recent edition of WHO Classification of hematologic neoplasms. It usually affects patients older than 60 years of age and carries a poor survival. Human T-lymphotrophic virus type 1 (HTLV-1) is a retrovirus that induces immunosuppression, has been associated with the development of adult T-cell leukemia/lymphoma, and has a high prevalence in Peruvian population. Aim: The goal of this retrospective study was to evaluate the HTLV-1 serological status in EBV-positive DLBCL Peruvian patients. Methods: We identified untreated patients with a diagnosis of DLBCL between January 2002 and June 2015 from the medical records of our institution. IRB approval was obtained prior to data collection. HTLV-1 positivity was defined based on Western Blot analysis. EBV-positivity was defined by identifying at least 10% EBV-encoded RNA (EBER) expression by chromogenic in situ hybridization in the pathological sample. Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the immunohistochemical expression of CD20, PAX5, BCL6, CD10, CD30 and MUM-1/IRF4 for re-classification purposes. Results: A total of 210 patients with DLBCL were identified. Of these, 11 patients (5%) were HTLV-1 seropositive and 199 (95%) were HTLV-1 seronegative. Thirty-two patients (15%) were EBV-positive by expression of EBER and 178 (85%) were EBV-negative. HTLV-1 positivity was found in 4/32 (12.5%) of EBV-positive DLBCL patients, and in 7/178 (4%). The odds ratio for HTLV-1 positivity in EBV-positive DLBCL was 3.5 (95% CI 0.7-14.7; p=0.045) when compared with the EBV-negative group. The median age of the HTLV-1-positive DLBCL patients was 65 years (range 45-85 years). There were 5 (45%) men and 6 women (55%). ECOG was >1 in 5 patients (45%), LDH was elevated in 8 (73%), extranodal disease in 7 (64%), and advanced clinical stage (III and IV) in 7 (64%). High IPI score (3-5 factors present) was seen in 8 patients (73%). Interestingly, all the patients who were EBV-positive and HTLV-1-positive presented with early stage (I and II), normal LDH levels and low IPI scores (0-2 factors). Conclusions: There is a high prevalence of HTLV-1 seropositive status in patients with EBV-positive DLBCL. Patients with double EBV and HTLV-1 positivity appear to present at earlier stages and with lower risk disease. Larger studies are needed to confirm these findings. Disclosures No relevant conflicts of interest to declare.

scholarly journals Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

2012 ◽  
Vol 30 (28) ◽  
pp. 3452-3459 ◽  
Author(s):  
Nathalie A. Johnson ◽  
Graham W. Slack ◽  
Kerry J. Savage ◽  
Joseph M. Connors ◽  
Susana Ben-Neriah ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
Molecular Subtype ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Bcl2 Protein ◽  
Large B Cell

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.

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

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.

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

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

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

2008 ◽  
Vol 49 (8) ◽  
pp. 1501-1509 ◽  
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

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

Haematologica ◽  
2020 ◽  
Vol 105 (11) ◽  
pp. 2667-2670 ◽  
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

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

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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