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

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 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.

scholarly journals Increased Expression of EZH2 Is Associated with Inferior Survival in Primary Central Nervous System Diffuse Large B-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4216-4216
Author(s):  
Briana Gibson ◽  
Rahul Matnani ◽  
Zheng Ping ◽  
Balabhadrapatruni VSK Chakravarthi ◽  
Yang Yang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Outcome ◽  
Protein Expression ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Primary central nervous system lymphomas (PCNSL) are rare and aggressive diseases with a poorly understood biology. Due to clinical heterogeneity and lack of prognostic biomarkers, effective and less toxic therapies are yet to be discovered. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was demonstrated to regulate cancer cell fate in response to DNA damage. EZH2 has been shown to be frequently overexpressed in various human cancers including lymphoma and is associated with inhibition of apoptosis through trimethylation of histone H3 lysine 27 (H3K27me3). The runt-related transcription factor 3 (RUNX3) is a downstream effector of the transforming growth factor-β (TGF-β) signaling pathway, and is critical for promoting cell death and apoptosis. Various studies have shown RUNX3 downregulation as a result of EZH2 upregulation. We investigated the EZH2 and RUNX3 protein expression and its impact on clinical outcome in PCNSL. Methods: A retrospective clinicopathologic chart review was conducted and 33 cases with diagnosis of PCNSL at our institution were included. Cases of secondary CNS involvement by diffuse large B-cell lymphoma (DLBCL) and HIV-related PCNSL were excluded. A tissue microarray (TMA) was constructed using archived formalin-fixed-paraffin-embedded tissue from 33 PCNSL cases. EZH2 and RUNX3 protein expression was assessed using immunohistochemistry and the staining was specifically classified based on percentage of the cells staining: 0 (<10%), 1+ (10-30%), 2+ (30-75%) and 3+ (>75%) and staining intensity: negative, weak positive and strong positive. Overall survival (OS) was calculated using the Kaplan-Meier method and log-rank test. Chi-square test was used to determine relationships between immunophenotypic subtype and protein expressions. Results: EZH2 and RUNX3 protein expression results were obtained in 25 out of 33 cases. The median age was 65 years (range 51-86 years) with a male:female ratio of 4:1. The majority of the cases were non-germinal center subtype (n=16, 64%) while the remaining 16% were germinal center subtype (n=9). Median OS was 11 months (range 2-120 months). Six out of 25 cases showed 3+ and strong staining for EZH2 while five cases were 2+, two were 1+ and the remaining was negative. The staining profile and number of cases for RUNX3 are as follows; 3+: seven, 2+: four, 1+: four, 0: 10. Strong and diffuse (3+) expression of EZH2 strongly correlated with inferior outcome (P=0.0045), independent of immunophenotypic subtype, while there was no significant correlation between OS and 0-2+ EZH2 expression. RUNX3 staining did not correlate with clinical outcome (P=0.67). Conclusions: Our data suggests a role of EZH2 overexpression in the pathogenesis of PCNSL. Overexpression of EZH2 appears to be an adverse prognostic factor and a potential target in PCNSL. Larger scale studies are warranted to elucidate the biology and prognostic utility of EZH2 in PCNSL. Disclosures No relevant conflicts of interest to declare.

scholarly journals Pathophysiological significance and therapeutic targeting of germinal center kinase in diffuse large B-cell lymphoma

Blood ◽  
2016 ◽  
Vol 128 (2) ◽  
pp. 239-248 ◽  
Author(s):  
Julie Marie Matthews ◽  
Shruti Bhatt ◽  
Matthew P. Patricelli ◽  
Tyzoon K. Nomanbhoy ◽  
Xiaoyu Jiang ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Therapeutic Targeting ◽  
Large B Cell Lymphoma ◽  
Key Points ◽  
Large B Cell

Key Points GCK signaling is activated in DLBCL, and this signaling is important to DLBCL proliferation and survival. Therapeutic targeting of GCK is feasible and may advance efforts to cure DLBCL patients.

scholarly journals UCH-L1 is induced in germinal center B cells and identifies patients with aggressive germinal center diffuse large B-cell lymphoma

Blood ◽  
2016 ◽  
Vol 127 (12) ◽  
pp. 1564-1574 ◽  
Author(s):  
Tibor Bedekovics ◽  
Sajjad Hussain ◽  
Andrew L. Feldman ◽  
Paul J. Galardy
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Neuronal Marker ◽  
Large B Cell Lymphoma ◽  
Increased Risk ◽  
Key Points ◽  
Poor Outcomes ◽  
Large B Cell

Key Points The neuronal marker UCH-L1 is induced in, and specifically augments the oncogene-induced transformation of, GCB cells. High levels of UCHL1 identify patients with GC DLBCL with an increased risk for poor outcomes.

scholarly journals Outcome of R-CHOP or CHOP Regimen for Germinal Center and Nongerminal Center Subtypes of Diffuse Large B-Cell Lymphoma of Chinese Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ying Huang ◽  
Sheng Ye ◽  
Yabing Cao ◽  
Zhiming Li ◽  
Jiajia Huang ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Survival Data ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Chinese Patients ◽  
First Line ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) can be molecularly subtyped as either germinal center B-cell (GCB) or non-GCB. The role of rituximab(R) in these two groups remains unclear. We studied 204 patients with de novo DLBCL (107 treated with first-line CHOP; 97 treated with first-line R-CHOP), patients being stratified into GCB and non-GCB on the basis of BCL-6, CD10, and MUM1 protein expression. The relationships between clinical characteristics, survival data, and immunophenotype (IHC) were studied. The 5-year overall survival (OS) in the CHOP and R-CHOP groups was 50.4% and 66.6% (P=0.031), respectively. GCB patients had a better 5-year OS than non-GCB patients whether treated with CHOP or not (65.0% versus 40.9%;P=0.011). In contrast, there is no difference in the 5-year OS for the GCB and non-GCB with R-CHOP (76.5% versus 61.3%;P=0.141). In non-GCB subtype, additional rituximab improved survival better than CHOP (61.3% versus 40.9%;P=0.0303). These results indicated that addition of rituximab to standard chemotherapy eliminates the prognostic value of IHC-defined GCB and non-GCB phenotypes in DLBCL by improving the prognostic value of non-GCB subtype of DLBCL.

Sign in / Sign up

Export Citation Format

Share Document