scholarly journals Accurate Classification of Diffuse Large B-Cell Lymphoma into Germinal Center and Activated B-Cell Subtypes Using a Nuclease Protection Assay on Formalin-Fixed, Paraffin-Embedded Tissues

2011 ◽  
Vol 17 (11) ◽  
pp. 3727-3732 ◽  
Author(s):  
Lisa M. Rimsza ◽  
George Wright ◽  
Mark Schwartz ◽  
Wing C. Chan ◽  
Elaine S. Jaffe ◽  
...  
2014 ◽  
Vol 167 (2) ◽  
pp. 281-285 ◽  
Author(s):  
Angela M. B. Collie ◽  
Jörk Nölling ◽  
Kiran M. Divakar ◽  
Jeffrey J. Lin ◽  
Paula Carver ◽  
...  

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3111-3111 ◽  
Author(s):  
Betty J. Glinsmann-Gibson ◽  
Dennis E McMillan ◽  
Sarah Wilkinson ◽  
Julie Teruya-Feldstein ◽  
Lisa M. Rimsza

Abstract Abstract 3111 Diffuse Large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. The Leukemia Lymphoma Molecular Profiling Project (LLMPP) collaboration has done extensive work regarding this disease including gene expression profiling to show that the cell of origin impacts the prognosis of the patient. Those cases which arise from an activated B cell (ABC) have a worse prognosis than those cases which arise from a germinal center B cell (GCB). We have used a subset of cases from our institution which have had gene expression profiling performed on frozen material and assigned ABC (n=18) or GCB (n=24) status (Rosenwald et al NEJM 2002, 346:1937). We have used matched formalin fixed paraffin embedded (FFPE) tissue block from these cases to obtain a microRNA profile utilizing the qNPA technology (High ThroughPut Genomics) as previously published (Roberts et al Lab Invest 2007, 87:979). This novel FFPE based RNAase protection assay measured 688 human microRNAs. Each microRNA was represented twice on the array and the values averaged for a signal value. The data were normalized to the total signal of the microarray. We were able to define a signature of increased microRNA for each DLBCL subtype as shown in Table 1. ABC subtype GCB subtype hsa-miR-155 hsa-miR-28-5p hsa-miR-196a hsa-miR-138 hsa-miR-501-3p hsa-miR-151-3p hsa-miR-656 hsa-miR-151-5p hsa-miR-1247 hsa-miR-182 hsa-miR-210 hsa-miR-613 The hsa-miR-155 is of importance in lymphoma as it regulates the generation of immunoglobulin class-switch in plasma cells (Turner et al Immunity 2007, 27:847) and was previously identified as a characteristic of ABC cell lines (Lossos et al Blood 2009,113:3754). The hsa-miR-210 has been shown to modulate the MYC antagonist MNT which allows for MYC expression (Grandori et all Cell Cycle 2009, 8:2756). This microRNA profile provides an opportunity to further explore the role microRNA plays in lymphoma biology and in particular, in DLBCL subtype determination. The success of the technique in FFPE tissue holds promise for further microRNA studies on archival material. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2018 ◽  
Vol 132 (22) ◽  
pp. 2319-2320 ◽  
Author(s):  
Megan S. Lim

In this issue of Blood, Mottok et al1 demonstrate the utility of a molecular assay that assesses the expression of 58 genes to distinguish primary mediastinal B-cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL) by using routinely available formalin-fixed paraffin-embedded tissue (FFPET) biopsies. The results could improve diagnostic accuracy for patients with PMBCL and may have important implications for clinical trial selection and interpretation of clinical outcomes for patients with this rare form of lymphoma.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5197-5197
Author(s):  
Hua Zhong

Abstract Abstract 5197 Introduction Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that accounts for nearly 40% of all lymphoid tumors. Both miR-155 and miR-146a expression levels are suggested to be regulated by NF-KB expression in DLBCL. In present study, the expression of miR-155 and miR-146a were investigated to evaluate the prognosis in DLBCL patients. Patients and Methods The expression levels of miR-155 and miR-146a in formalin-fixed/paraffin-embedded tissue of patients with DLBCL (n=50) have been compared with reactive hyperplasia lymphoid nodes (n=20) by using real-time polymerase chain reaction. Clinical characters of patients such as LDH, β2-MG, International Prognostic Index (IPI), ECOG score and c-myc expression levels have also been investigated. Results 1) The expression levels of miR-155 and miR-146a were significantly higher in DLBCL patients than control (P<0.001). (Fig 1) 2) The expression levels of miR-155 and miR-146a were different between germinal center B-cell like DLBCL (GCB-DLBCL) and activated B-cell-like DLBCL (ABC-DLBCL), but the difference had no significance (P>0.05). 3) There was correlation between the expression of miR-155 and miR-146a in DLBCL patients (r =0.639, P<0.001). 4) There was positive correlation in the expression of miR-146a with LDH, β2-MG, IPI, ECOG score and c-myc expression levels in DLBCL patients. 5) Lower expression levels of miR-155 and miR-146a were found to be associated with high complete remission (CR) rate and overall response (OR) rate in DLBCL patients (P<0.05). 6) Lower expression levels of miR-146a in DLBCL patients were only associated with better 5 years progression free survival (5y-PFS) (P=0.044), but lower expression levels of miR-155 in DLBCL patients were associated with better 5y-PFS (P=0.013) and 5 years overall survival (5y-OS) (P=0.007). 7) Multivariate analysis using a Cox proportional hazard model confirmed that either miR-155 or miR-146a was the independent predictor. (For miR-155 5y-PFS, Hazards ratio 0.260, 95% CI, 0.058–0.801; for miR-146a 5y-PFS, Hazards ratio 0.251, 95% CI, 0.068–0.922) 8) Compared to CHOP protocol, the higher miR-155 expression level patients who chose R-CHOP protocol for treatment achieved better 3y-PFS and 3y-OS (P<0.05). Conclusions The expression levels of miR-155 and miR-146a were higher in DLBCL patients. Moreover, high expressions of these two microRNAs were associated with the disease progression. Patients with higher miR-155 expression levels may be benefit from the protocol including Rituximab. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3425-3433 ◽  
Author(s):  
Lisa M. Rimsza ◽  
Michael L. LeBlanc ◽  
Joseph M. Unger ◽  
Thomas P. Miller ◽  
Thomas M. Grogan ◽  
...  

Abstract Gene expression profiling (GEP) on frozen tissues has identified genes predicting outcome in patients with diffuse large B-cell lymphoma (DLBCL). Confirmation of results in current patients is limited by availability of frozen samples and addition of monoclonal antibodies to treatment regimens. We used a quantitative nuclease protection assay (qNPA) to analyze formalin-fixed, paraffin-embedded tissue blocks for 36 previously identified genes (N = 209, 93 chemotherapy; 116 rituximab + chemotherapy). By qNPA, 208 cases were successfully analyzed (99.5%). In addition, 15 of 36 and 11 of 36 genes, representing each functional group previously identified by GEP, were associated with survival (P < .05) in the 2 treatment groups, respectively. In addition, 30 of 36 hazard ratios of death trended in the same direction versus the original studies. Multivariate and variable cut-off point analysis identified low levels of HLA-DRB (< 20%) and high levels of MYC (> 80%) as independent indicators of survival, together distinguishing cases with the worst prognosis. Our results solve a clinical research problem by demonstrating that prognostic genes can be meaningfully quantified using qNPA technology on formalin-fixed, paraffin-embedded tissues; previous GEP findings in DLBCL are relevant with current treatments; and 2 genes, representing immune escape and proliferation, are the common features of the most aggressive DLBCL.


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