Immunohistochemical Expression Patterns of Germinal Center and Activation B-cell Markers Correlate With Prognosis in Diffuse Large B-cell Lymphoma

2004 ◽  
Vol 28 (4) ◽  
pp. 464-470 ◽  
Author(s):  
Chung-Che Chang ◽  
Sara McClintock ◽  
Ronald P Cleveland ◽  
Trent Trzpuc ◽  
David H Vesole ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Immunohistochemical Expression ◽  
Cell Markers ◽  
Large B Cell Lymphoma ◽  
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.

Immunohistochemical Expression Pattern of Germinal Center and Non-Germinal Center Markers Correlates with Prognosis in Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4636-4636
Author(s):  
Carlos Chiattone ◽  
Marineide P. Carvalho ◽  
Roberto P. Paes ◽  
Karina C.B. Ribeiro ◽  
Fernando Soares
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Immunohistochemical Expression ◽  
Molecular Features ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Recent studies have shown correlations between diffuse large B-cell lymphoma (DLCBL) prognosis and molecular features using genome profiles by cDNA microarrays. Since this analysis is not routinely used, immunohistochemical tests for prediction of DLBCL survival are gaining major importance, using markers as, CD10, BCL-6 and MUM-1 to identify germinal center B-cell (GCB) and non-GCB, respectively. The goal of this study was to evaluate the significant effect on survival within GCB and non-GCB subgroup. Patients and Methods: Seventy-four untreated pts (median age: 58 yrs: 38M/36F) with DLBCL de novo diagnosed in a single institution, treated with CHOP-like regimens. Tissue microarrays (TMA) blocks were created from paraffin-embedded, formalin-fixed block and stained with antibodies to CD20 (clone L26, Dako), CD10 (clone 56C6; Novocastra; NCL-CD10-270), BCL-6 (clone GI 191E/A8; Cell Mark; CMC 798) and MUM1 (clone MUM1p; Dako, CA; M7259). Results. Cases were subclassified using CD10, BCL-6, and MUM1 expression, and 25 cases (33.8%) were considered GCB and 49 cases (66.2%) non-GCB. The 2-year overall survival (OS) for the GCB group was 80% compared with only 38.9% for the non-GCB (p<0.001). In the multivariate analysis, only the International Prognostic Index score (IPI 3-4 HR=2.6, p=0.013) and the GCB phenotype (Non-GCB HR=2.7, p=0.054) were independent prognostic factors. In summary, immunohistochemical expression of CD10, BCL-6 and MUM1 are able to determine the GCB and non-GCB subtypes of DLBCL and predict survival.

Distinct Expression Patterns of microRNAs in Activated B Cell (ABC) and Germinal Center B (GC) Subtypes of Diffuse Large B Cell Lymphoma (DLBLC).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 562-562
Author(s):  
Jean-Noel Bastie ◽  
Jean-Philippe Jais ◽  
Thierry Molina ◽  
Emmanuelle Come ◽  
Bertrand Coiffier ◽  
...  
Keyword(s):  
B Cell ◽  
Mirna Expression ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Rt Pcr ◽  
Large B Cell Lymphoma ◽  
Micro Rnas ◽  
Large B Cell

Abstract The Micro RNAs (miRNAs) are small non-coding, single-stranded RNAs that regulate the expression of genes by hybridizing the mRNA target with complementary sequences that are followed by translational repression, mRNa cleavage or destabilization. There is evidence that miRNA play an important role in carcinogenesis. Aberrant miRNA expression has been found in a variety of human malignancies including B-cell leukemias and lymphomas. The purpose of this study is to determine the miRNA expression patterns in DLBCL and their relationship with clinical characteristics and outcome. We used high throughput quantitative RT-PCR technology (Taqman Low density Arrays) to analyze the expression profile of 365 different mature miRNA in 12 Diffuse Large B-Cell Lymphoma (DLBCL) samples which had been previously characterized at the transcriptional level with Affymetrix HU133A micro-arrays. MiR-155 expression was significantly lower in the 6 samples with a Germinal Center (GC) mRNA profile than in the 6 samples with an Activated B-Cell (ABC) profile. Expression of miR-155 and of different miRNA involved in lymphoid differentiation (miR-181a, miR127) or tumour pathogenesis (cluster miR 17–92) were further evaluated in a series of 64 patients with DLBCL treated with Rituximab associated with chemotherapy (R-CHOP). 28 patients had been enrolled in the LNH98.5 GELA trial between February 1998 and February 2000 and 36 were treated with R-CHOP in GELA centers after the closure of the LNH98-5 trial, between November 2000 and June 2004. The median follow up of these patients is 69 months. Patients median age at diagnosis was 69 years (range 59–82) and 28 patients presented with an International Prognostic Index (IPI) score of more than 3. Mature miRNA expression was determined by quantitative RT-PCR with Applied Biosystems specific miRNA primer and probe sets and normalized to U6 small nuclear RNA expression. MiR-155 expression was significantly higher in patients with a lymphoma of the ABC subtype, defined on the basis of the transcriptional profile (mean delta Ct = − 3.9 in the 41 ABC samples, mean delta Ct = − 1.67 in the 23 GC samples, p<0.00001) and significantly higher in patients with a high (4 or 5) IPI score (p=0.02). A high miR-155 expression was associated with a trend towards a poorer overall survival. The expression of miR-127, miR-181a and the cluster 17–92 were not correlated with clinical outcome. These analyses are currently being extended to a larger series of patients in order to determine whether other miRNA can be used to classify DLBCL samples into ABC and GC subtypes and whether some miRNA have prognostic significance in the era of treatments combining Rituximab and chemotherapy.

Immunohistochemical Expression Patterns of Germinal Center and Activation B-Cell Markers in Diffuse Large B-Cell Lymphoma. Clinicopathologic Study of 62 Cases from Peru.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4646-4646
Author(s):  
Shirley Quintana ◽  
Carlos Barrionuevo ◽  
Henry Gomez ◽  
Silvia Neciosup ◽  
Oswaldo Grados ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
B Cell Lymphoma ◽  
Immunohistochemical Expression ◽  
Cell Markers ◽  
Cell Pattern ◽  
Large B Cell Lymphoma

Abstract Background: Recent studies have shown that diffuse large B-cell lymphoma (DLBCL) cases with gene expression profiles similar to germinal center (GC) B cells had a much better prognosis than DLBCL cases with gene expression profiles resembling activated B cells. DLBCL can be classified into three immunohistochemical expression patterns: GC B-cell pattern (pattern A) expressing CD10 and/or Bcl-6 but not MUM1; activated GC B-cell pattern (pattern B) expressing at least one of GC B-cell markers and MUM1; and activated non-GC B-cell pattern (pattern C) expressing MUM1 but not GC B-cell markers. Purpose: To determine the frequency of these patterns, the immunohistochemical expression intensity of MUM1, BCL6 and BCL2, as well as International Prognostic Index (IPI) and therapeutical response. Methods: Immunohistochemical analysis on paraffin-embedded tissues was performed using the streptavidin-avidin-biotin method in 62 cases of DLBCL. The intensity of immunohistochemical expression was performed as follows: positive (more than 50% expression), positive/negative (expression 20 to 50%), and negative (less than 20%expression). Results: The average age was 60 years. Females were slightly more frequent than males. 84% cases were primary nodal. According to IPI, 60% of cases were low (L) or intermediate-low (IL) risk, and 40% were intermediate-high (IH) or high risk (H). The corresponding A, B and C patterns, by immunohistochemistry, were 10%, 19% and 65% respectively. The majority of patients were treated with CHOP. Complete response (CR) was achieved in 54%, partial response (PR) in 11%, and no response (NR) in 23%. 9 % were not assessed. 4/6, 8/10, 17/36 of the cases had CR in the patterns A, B, C respectively. 5/6, 8/12, 22/40 of the cases were L-IL in the same patterns, without significant difference between these groups. The immunohistochemical expression intensity for either marker was not statistically significant. Conclusions: The most frecuent pattern was C. The activated patterns were most common. The correlation between different pattern expression, IPI and therapeutical response didn’t show statistical differences, probably due to the small size of the sample.

Immunohistochemical Expression of Germinal Center and Non-Germinal Center Markers in Primary Gastric Diffuse Large B-Cell Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5276-5276
Author(s):  
Fernando Hurtado ◽  
Brady Beltran ◽  
Luis Riva ◽  
Renzo Salas ◽  
Domingo Morales ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Immunohistochemical Expression ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract BACKGROUND: Recent studies have shown a correlation between diffuse large B-cell lymphoma (DLCBL) prognosis and molecular features using genome profiles by cDNA microarrays. Later reports have shown that immunohistochemical tests using markers as CD10, bcl-6 and MUM-1 to identify germinal center B-cell (GCB) and non-GCB patterns can have a similar value and are gaining major importance in assessing prognosis in patients with DLBCL. Gastric DLCBL is the most frequent extranodal non-Hodgkin lymphoma. AIM: To evaluate the frequency of GCB and non-GCB subgroups in primary gastric DLCBL and the impact of these tests in prognosis. PATIENTS AND METHODS: Patients older than 18 years with a diagnosis of primary gastric DLBCL were identified in a single institution from January 2002 to December 2005 and included in this analysis. Immunohistochemical stains were performed using antibodies against CD20, CD10, bcl-6 and MUM1 in all cases. Survival curves were obtained using the Kaplan-Meier method. RESULTS: Twenty-nine patients were included in this study. The median age at diagnosis was 68 years (range 40 to 86 years). Thirteen male and 16 female patients were included. All cases received chemotherapy with CHOP regimen. Cases were subclassified in GCB and non-GCB using CD10, bcl-6, and MUM1 expression. Four cases (14%) were considered GCB and 25 cases (86%) non-GCB. There were no statistical differences between both groups in the following variables: age, ECOG performance status, serum LDH levels, clinical stage and International Prognostic Index (IPI) score. No statistical difference in survival was observed between the GCB and non-GCB groups. The 3-year overall survival for the entire group was 30%. CONCLUSION: Immunohistochemical expression of non-GCB pattern is very frequent in primary gastric DLBCL in Peru. However, it does not show an effect in survival, probably related to the small number of cases included in the present study.

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.

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