Fas or Fas Ligand Expression Can Determine the Clinical Outcome of Germinal Center Type in Diffuse Large B Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3267-3267
Author(s):  
Yasushi Kojima ◽  
Hisashi Tsurumi ◽  
Naoe Goto ◽  
Michio Sawada ◽  
Toshiki Yamada ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Germinal Center ◽  
Fas Ligand ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Type 3 ◽  
Large B Cell

Abstract In recent years, diffuse large B cell lymphoma (DLBCL) has been classified by a cDNA microarray, an oligonucreotide microarray, or a tissue microarray. From the prognostic point of view, DLBCL consists of germinal center B-cell-like (GC) type, activated B-cell-like (ABC) type and type 3. ABC type and type 3 can be collectively categorized as non-GC (NGC) type. GC type has favorable prognosis compared with NGC type. Escape from apoptosis is considered to be an important mechanism for the progression of lymphoma. Fas is the major protein which leads to apoptosis by binding with Fas-ligand (FasL). We evaluated the prognostic significance of such markers as CD10, Bcl-6, MUM1, Fas and FasL, as well as GC or NGC type with paraffin embedded sections from 69 DLBCL patients immunohistochemicaly. The patients were 40 men and 29 women with median age of 67 years old (range, 20–82 years old). The median follow-up of surviving patients was 43 months. The 3-year OS for the entire group was 56%. There was no significant difference in sex, age, clinical stage, lactate dehydrogenase, or International Prognostic Index between GC and NGC type. Expression of CD10 was seen in 29% (20 of 69 of the patients), Bcl-6 in 27% (19 of 69), MUM1 in 27% (19 of 69), Fas in 51% (36 of 69), and FasL in 50% (35 of 69). We divided 69 DLBCLs to 26 GC type (CD10 positive or Bcl-6 positive and MUM1 negative) and 43 NGC type (the other). Positive CD10 was the best marker to indicate favorable overall survival (p=0.0156). GC type had tendency to have better overall survival than NGC type, though it was not significant (p=0.0723). Although Fas or FasL expression was not significant for overall survival in all DLBCL, it predicted significantly a longer over all survival (Fas; p=0.0021, FasL; p=0.0165) in GC type. These results may suggest that the presence of a subtype of DLBCL in which Fas/FasL system works effectively. This group is approximately 20% of DLBCL and mainly belongs to the GC type. Fas expression in GC type of DLBCL may predict the prognosis and be useful to choose the appropriate therapy. Furthermore, CD10 was more significant than GC type and, thus, we may need to build the strict consensus for GC type.

LMO2 and Bcl-6 Expression in Diffuse Large B-Cell Lymphoma Predict Overall Survival in R-CHOP Treated Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5304-5304
Author(s):  
Heather D. Brooks ◽  
Robert M. Graham ◽  
Randall L. Woodford ◽  
Audrey K. Bennett ◽  
Xin Qun Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
Previous History ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract LMO2, a germinal center marker and transcription factor with an important role in angiogenesis and erythropoiesis, was found to confer improved prognosis in diffuse large B-cell lymphoma (DLBCL) when expressed in tissue microarray (TMA) samples (Natkunam et al J Clin Oncol2008,26:447). Bcl-6, a transcriptional repressor controlling germinal center formation, has been associated with favorable outcomes in DLBCL patients treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) but was found to have no prognostic significance in DLBCL patients older than 60 treated with rituximab (R) + CHOP (Winter et al Blood2006,107:4207). Hans previously described an algorithm to subclassify DLBCL into germinal center B-cell like (GCB) and activated B-cell like (ABC) using immunohistochemical staining for CD10, bcl-6 and MUM1 with GCB exhibiting improved survival (Hans et al Blood2004,103:275). The aim of this study was to evaluate the prognostic value of LMO2, CD10, bcl-6, bcl-2 and MUM1 expression in DLBCL patients treated with R-CHOP. We also applied the Hans classification to our cohort and incorporated LMO2 into the algorithm. Adults (>18 years) with DLBCL who were diagnosed and treated at the University of Virginia between 2000 and 2007 were retrospectively evaluated. Patients were selected based on adequate tissue, treatment with at least 3 cycles of R-CHOP and if a minimum of 6 months of follow-up data was available at the time of data analysis. Forty-one cases were included of which 26 were de novo DLBCL, 12 were DLBCL with concurrent follicular lymphoma (FL) and 3 cases were new diagnoses of DLBCL with a previous history of FL. H&E-stained sections from paraffin-embedded, formalin-fixed blocks were used to define diagnostic areas, and 3 representative 1.0-mm cores were obtained from each case. TMA sections were then stained with antibodies to CD10, bcl-6, bcl-2, MUM1 and LMO2. Cases were assigned to GCB-like and ABC-like subgroups based on the Hans algorithm. The LMO2 stain was incorporated into the Hans algorithm to create modified-Hans (m-Hans) subgroups; the sample received an m-GCB designation if LMO2 positive but the normal Hans classification was applied if the sample was LMO2 negative. For 41 complete patient samples, a nonparametric Kaplan-Meier estimator was used to estimate overall survival (OS) probability for each group (m-GCB, m-ABC). A log-rank test demonstrated that there was a significant difference in OS probability between m-ABC and m-GCB groups (p = 0.047). Six month and 3 year survival for m-ABC and m-GCB were 71% and 88%, and 44% and 68% respectively. A semi-parametric Cox proportional hazard model was used to assess association between OS and each individual stain (CD10, bcl-2, bcl-6, MUM1 and LMO2), and a hazards ratio was used to quantify the effect of each stain. Bcl-6 and LMO2 expression were highly correlated, with bcl-6 expression significantly associated with OS (p=0.011). Patients without bcl-6 expression had more than four-fold risk than those expressing bcl-6 in OS (Hazard Ratio = 4.29, 95% CI: 1.4–13.1). Also, LMO2 expression showed a marginal association with OS (p=0.065). In conclusion, LMO2 incorporated into the Hans classification and bcl-6 expression are both significant predictors of OS in DLBCL patients treated with R-CHOP. Figure Figure

Addition of Rituximab to CHOP Regimen Improves Clinical Outcome in Non-Germinal Center Type Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4725-4725
Author(s):  
Masahiro Yokoyama ◽  
Daisuke Ennishi ◽  
Kyoko Ueda ◽  
Makoto Kodaira ◽  
Shuhei Yamada ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Chop Regimen ◽  
Large B Cell Lymphoma ◽  
Type 3 ◽  
Large B Cell

Abstract Background: In recent years, diffuse large B-cell lymphoma (DLBCL) has been classified into the germinal center B-cell (GC) type, the activated B-cell (ABC) type, and the type 3 using global gene expression profiling or immunohistochemical staining. It has been reported that the GC type DLBCL showed significantly longer survival than the non-GC (ABC and the type 3) type DLBCL treated with CHOP or CHOP like regimen not using rituximab. Methods: We analyzed retrospectively the prognosis between the GC and non-GC types of DLBCL treated with R-CHOP regimen. All 50 patients with DLBCL, diagnosed between July 2003 and July 2005 were included in this study. The pathology was reviewed by hematopathologist and confirmed to be de novo DLBCL according to the WHO classification. Patients with primary CNS- and post-transplant lymphomas were excluded. GC type or non-GC type DLBCL was determined by immunohistochemistry such as the expression patterns of CD10, BCL-6, and IRF-4 (MUM1). All patients were initially treated with six cycles of R-CHOP regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. If we evaluated partial response after six cycles of R-CHOP, the patients have added radiation therapy. Results: The patients consisted of 30 GC type and 20 non-GC type DLBCL with a median age of 61.0 yr (range 31–83 yr). The median follow up of surviving patients was 24 months. CR rate between GC and non-GC types were 57.0% vs. 75.0%, p=0.186, and overall response rate were 87.0% vs. 90.0%, p=0.929, respectively. The median of progression free survival was 17.3 months vs. 19.6 months, p=0.80. There is no statistical significance difference between two groups. Conclusion: These results suggest that addition of rituximab to CHOP regimen improves clinical outcome of non-GC type DLBCL as well as GC type DLBCL.

Fas and Fas ligand expression on germinal center type-diffuse large B-cell lymphoma is associated with the clinical outcome

2006 ◽  
Vol 76 (6) ◽  
pp. 465-472 ◽  
Author(s):  
Yasushi Kojima ◽  
Hisashi Tsurumi ◽  
Naoe Goto ◽  
Masahito Shimizu ◽  
Senji Kasahara ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Germinal Center ◽  
Fas Ligand ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Ligand Expression ◽  
Large B Cell

scholarly journals Identification of super enhancer-associated key genes for prognosis of germinal center B-cell type diffuse large B-cell lymphoma by integrated analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xi Li ◽  
Yan Duan ◽  
Yuxia Hao
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Integrated Analysis ◽  
Cell Type ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Large B Cell

Abstract Background The pathogenesis of germinal center B-cell type diffuse large B-cell lymphoma (GCB-DLBCL) is not fully elucidated. This study aims to explore the regulation of super enhancers (SEs) on GCB-DLBCL by identifying specific SE-target gene. Methods Weighted gene co-expression network analysis (WGCNA) was used to screen modules associated with GCB subtype. Functional analysis was performed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. H3K27ac peaks were used to identify SEs. Overall survival analysis was performed using Kaplan–Meier curve with log-rank and Breslow test. The effect of ADNP, ANKRD28 and RTN4IP1 knockdown on Karpas 422 and SUDHL-4 cells proliferation was analyzed by CCK-8. Karpas 422 and SUDHL-4 cells were treated with bromodomain and extra-terminal domain (BET) inhibitor JQ1, and the expression of ADNP, ANKRD28 and RTN4IP1was measured by qRT-PCR. Results A total of 26 modules were screened in DLBCL. Turquoise module was closely related to GCB-DLBCL, and its eigengenes were mainly related to autophagy. There were 971 SEs in Karpas 422 cell and 1088 SEs in SUDHL-4 cell. Function of the nearest genes of overall SEs were related to cancer. Six SE-related genes associated with GCB-DLBCL were identified as prognostic markers. Knockdown of ADNP, ANKRD28 and RTN4IP1 inhibited the proliferation of Karpas 422 and SUDHL-4 cells. JQ1 treatment suppressed ADNP, ANKRD28 and RTN4IP1 expression in Karpas 422 and SUDHL-4 cells. Conclusions A total of 6 SE-related genes associated with GCB-DLBCL overall survival were identified in this study. These results will serve as a theoretical basis for further study of gene regulation and function of GCB-DLBCL.

BCL6 Rearrangement Detected by FISH Analysis Is a Poor Prognostic Factor in the “Non-Germinal Center Phenotype” of Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4620-4620
Author(s):  
Jun Takizawa ◽  
Sadao Aoki ◽  
Akihito Momoi ◽  
Toshiki Kitajima ◽  
Masutaka Higashimura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Diffuse large B-cell lymphoma (DLBCL), which is the most common type of adult non-Hodgkin lymphoma, is considered to be heterogeneous in cytogenetics, immunophenotype and clinical feature. As the results of gene expression profiling, DLBCL can be divided into prognostically significant 3 subgroups of germinal center B-like (GCB), activated B-like and type 3. Chromosomal translocations affecting the BCL6 locus at the 3q27 locus are common in DLBCL, however, the prognostic significance of BCL6 rearrangement is still controversial. Methods: Twenty-six cases of DLBCL were examined with interphase fluorescence in situ hybridization (FISH) on touch preparations of lymph nodes using LSI BCL6 dual color probes (Vysis) for the incidence of BCL6 rearrangement and immunohistochemistry on paraffin section using CD10, BCL6 and MUM1 for subclassfying “GCB phenotype” and “non-GCB phenotype”. The correlation of BCL6 rearrangement with survival was investigated in two subgroups of DLBCL. Results: Of the 26 DLBCL cases, 6 cases (23%) were considered GCB phenotype and 20 cases (77%) non-GCB phenotype. BCL6 rearrangements were detected in 2 of 6 cases (33%) with GCB phenotype and 9 of 20 (45%) with non-GCB phenotype (total 11/26, 42%). ALL 6 cases with the GCB phenotype achieved sustained complete remission after chemotherapy and are alive. On the other hand, complete remission rate was 22% for the cases with BCL6 rearrangement but 73% for the cases without BCL6 rearrangement in the non-GCB phenotype (p=0.069). BCL6 rearrangement had a significant adverse effect on progression free survival within the non-GCB phenotype (P=0.016), but there was no significant correlation between BCL6 rearrangement and overall survival. Conclusion: FISH-based technique of the BCL6 rearrangements using touch preparations of lymph nodes could be developed for the retrospective analysis on survival. BCL6 rearrangement showed a poor prognostic effect particular in the non-GCB subgroup of DLBCL. Overall survival Overall survival Progression free survival Progression free survival

The Oncoprotein LMO2 Is Expressed in a Germinal Center B-Cell-Associated Pattern and Predicts Survival in Patients with Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 810-810
Author(s):  
Yasodha Natkunam ◽  
Eric D. Hsi ◽  
Christine Hans ◽  
Shuchun Zhao ◽  
Behnaz Taidi ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Rna Expression ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is clinically and molecularly heterogeneous and portends a poor prognosis in more than half the affected patients. We developed a multivariate model based on the RNA expression of six genes – LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2 – that independently predicts survival in DLBCL patients treated with anthracycline-containing regimens (Lossos et al, NEJM 2004). Since the transcription factor LMO2 emerged as the strongest predictor of superior outcome, we generated a monoclonal anti-LMO2 antibody in order to document the tissue expression pattern of LMO2 protein and to establish its prognostic significance. Immunohistological analysis of 1200 normal tissues and hematolymphoid neoplasms showed that LMO2 protein is expressed as a nuclear marker in normal germinal center (GC) B-cells and in a subset of B-cell lymphomas. It is rarely expressed in mature T, NK and plasma cell neoplasms. Immature precursors of all bone marrow hematopoietic lineages and a significant proportion of acute lymphomphoblastic and myeloid leukemias express LMO2 protein. Apart from endothelial cells, no other non-hematolymphoid tissues we tested showed LMO2 protein expression. Hierarchical cluster analysis of immunohistologic data in DLBCL demonstrated that the expression profile of LMO2 protein is similar to that of other GC-associated proteins (HGAL, BCL6 and CD10) but different from that of non-GC proteins (MUM1/IRF4 and BCL2). LMO2 protein expression paralleled its RNA expression in B-cell lymphoma cell lines and was found in GC B, but not in non-GC, B-cell lines. To test the prognostic significance of LMO2 protein we analyzed an independent cohort of 203 DLBCL patients (mean age 63, range 18–93), uniformly treated with anthracycline-containing chemotherapy not containing rituximab, from four medical centers. No significant difference in response to therapy (CR and CRu) was observed between patients with LMO2-positive and LMO2-negative lymphomas (77% and 59%, respectively, p 0.05). However, Kaplan- Meier curves demonstrated a statistically significant difference in overall survival (OS) between LMO2-positive and LMO2-negative cases (p 0.035; median OS of 74 and 20 months, respectively). Similarly, event-free survival (EFS) was also significantly longer in patients with LMO2-positive compared to LMO2-negative lymphomas (p 0.01, median EFS of 48 and 12 months, respectively). The predictive power of LMO2 expression was IPI-independent. Multivariate analyses with protein expression profiles of HGAL, BCL6, CD10, JAW1, MUM1/IRF4 and BCL2 on this cohort of patients are underway to construct a clinically applicable immunohistologic algorithm for predicting survival. The capacity of LMO2 protein to identify DLBCL patients with improved outcome in an IPI-independent manner indicates its important role in risk stratification in this disease.

scholarly journals CD30 Expression in Germinal Center B-cell-like and non-Germinal Center B-cell-like Subtypes of Diffuse Large B-cell Lymphoma

2020 ◽  
Vol 8 (B) ◽  
pp. 375-380
Author(s):  
Patricia Fransisca Julianty ◽  
Maria Francisca Ham ◽  
Kusmardi Kusmardi ◽  
Agnes Stephanie Harahap
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cross Sectional ◽  
Large B Cell Lymphoma ◽  
Cutoff Values ◽  
Germinal Center B Cell ◽  
Significant Difference ◽  
Large B Cell

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common and most heterogeneous type of non-Hodgkin lymphoma. With current therapeutic modalities, 30%–40% of DLBCL cases still experience recurrence. The discovery of CD30 expression in DLBCL in several studies has opened up alternative opportunities for new target therapies. AIM: This cross-sectional study aimed to determine CD30 expression in DLBCL and its difference in expression in germinal center B-cell such as (GCB) and non-GCB subtypes. METHODS: The sample consisted of 25 GCB and 25 non-GCB cases based on immunohistochemical examination performed at Cipto Mangunkusumo Hospital from 2014 to 2017. CD30 staining was carried out and assessed using tumor cells percentage with positive cutoff values of >0%, >10%, and >20%. RESULTS: Positive CD30 expression was obtained in 8 (16%), 4 (8%), and 3 (6%), out of 50 DLBCL cases with positive cutoff values of >0%, >10%, and >20%, respectively. We performed Fisher’s exact test to determine CD30 expression in the GCB and non-GCB subtypes and found no significant difference with p > 0.05. CONCLUSION: Our study found no significant difference between CD30 expression in the GCB and non-GCB subtypes of DLBCL.

scholarly journals PKM2 Expression Is Associated with Favorable Outcome in Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5319-5319
Author(s):  
Yongqiang Wei ◽  
Xiaolei Wei ◽  
Jialin Song ◽  
Weimin Huang ◽  
Hong Zeng ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Metabolic Reprogramming ◽  
High Expression ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract Pyruvate kinase muscle isoenzyme 2 (PKM2) is a key enzyme in aerobic glycolysis and thought to contribute to cancer cell metabolic reprogramming. The aim of this study was to evaluate whether PKM2 expression by immunohistochemical was a potential prognostic biomarker in diffuse large B-cell lymphoma (DLBCL) patients. Herein, we explore the expression of PKM2 by immunohistochemistry in all 87 patients diagnosed as de novo DLBCL according to WHO classification. Among all the 87 patients, high expression of PKM2 was observed in 20 cases (23.0%). There was no significant difference in gender, age, B symptoms, performance status, LDH, stage and IPI score between patients with high and low PKM2 expression(P>0.05). Patients with high PKM2 expression showed significant superiorevent-free survival, but only a tendency in overall survival compared with low PKM2 expression patients (p=0.047 and p=0.465, respectively). Multivariate analysis showed that high expression of PKM2, independent of the international prognostic index, implied a favorable event-free survival (HR=0.363; 95% CI=0.109-0.927, p=0.038), but not overall survival (HR=0.646; 95% CI= 0.185-2.254, p=0.493). In conclusion, these data suggest that the expression of PKM2 may implied a good outcome in DLBCL patients treated with R-CHOP. Disclosures No relevant conflicts of interest to declare.

Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Lluı́s Colomo ◽  
Armando López-Guillermo ◽  
Marı́a Perales ◽  
Susana Rives ◽  
Antonio Martı́nez ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Clinicopathological Features ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract To analyze the relationship between immunophenotyping profile and main clinicopathological features and outcome in diffuse large B-cell lymphoma (DLBCL), we studied 128 patients (59 men, 69 women; median age 65 years) consecutively diagnosed with de novo DLBCL in a single institution. Cells from each patient were immunostained with CD20, CD79a, CD5, CD10, bcl-6, MUM1, CD138, bcl-2, p53, p27, and Ki-67 antibodies. Four immunophenotyping profiles were distinguished according to the pattern of differentiation: germinal center–CD10+ (GC-CD10+; CD10+/Bcl-6+/MUM1−/CD138−), germinal center–CD10− (GC-CD10−; CD10−/Bcl-6+/ MUM1−/CD138−), post–germinal center (pGC; CD10−/bcl-6±/ MUM1+/CD138−), and plasmablastic (CD10−/bcl-6−/MUM1+/CD138+). Rearrangement of bcl-2 was studied by polymerase chain reaction (PCR) in 57 patients. Single-antigen expression was as follows: CD5, 2%; CD10, 21%; bcl-6, 72%; MUM1, 54%; CD138, 2%; bcl-2, 59%; p53, 28%; p27, 40%. Distribution according to differentiation profiles was as follows: GC-CD10+, 24 patients, GC-CD10-, 30 patients; pGC, 60 patients; plasmablastic, 2 patients; other patterns, 12 patients. The pGC profile was associated with primary nodal presentation and immunoblastic morphology, whereas GC-CD10+ tumors showed disseminated disease, centroblastic morphology, bcl-2 rearrangement, and lower Ki-67 proliferative index. GC-CD10− patients more often presented with primary extranodal origin, early stage, normal lactic acid dehydrogenase (LDH) levels, and low or low/intermediate International Prognostic Index (IPI) scores than the others. However, no significant difference was found in terms of response or overall survival (OS) according to these profiles. Expression of bcl-2 was associated with advanced stage, high or high-intermediate IPI, and poor OS. Expression of bcl-2 maintained predictive value in multivariate analysis, with stage and LDH. In conclusion, differentiation profile was associated with particular clinicopathological features but was not essential to predicting outcome in DLBCL patients.

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