CD30 Immunohistochemical Expression In Diffuse Large B-Cell Lymphoma Is Associated With Decreased Overall Survival and The Non-Germinal Center Molecular Subtype

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4318-4318 ◽  
Author(s):  
Angela M. B. Collie ◽  
Brian T. Hill ◽  
Elena A. Manilich ◽  
Mitchell R Smith ◽  
Eric D. Hsi
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Poor Prognosis ◽  
De Novo ◽  
Cell Lymphoma ◽  
Molecular Subtype ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Immunohistochemical Expression ◽  
Large B Cell Lymphoma

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease entity with multiple potential prognostic biomarkers. Cell of origin (COO) molecular subtype classification using gene expression profiling with microarrays and immunohistochemical expression of CD30 have been examined as potential prognostic markers, often with conflicting results. A recent study demonstrated that patients with CD30-positive DLBCL had better prognosis compared to patients with CD30-negative DLBCL and had a distinct gene expression profile (Hu S et al. Blood. 121(14): 2715-24, 2013). In addition, due to the development of targeted therapies such as an anti-CD30 monoclonal antibody drug conjugate, the identification and prognostic relevance of this biomarker has potential therapeutic impact. We evaluated CD30 expression, determined by immunohistochemistry, in a cohort of de novo DLBCL cases at our institution and examined cell of origin molecular subtype in the CD30-positive and CD30-negative groups. Design 94 adult patients with de novo DLBCL uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) as first line therapy were identified at The Cleveland Clinic. Clinical data was collected for these patients. A tissue microarray was created and stained with antibodies to CD10, CD20, CD30, BCL-6, and MUM-1. COO subtype was determined for the Hans algorithm in all cases. CD30 was considered positive when expression was seen in ≥ 20% of tumor cells. Results There were no significant differences in sex, age, IPI score, or stage between patients in the CD30-positive and CD30-negative groups. The median age of the DLBCL cohort was 63 years (range 17-91 years) with a male : female ratio of 1:1.1. 54% of patients had stage III or IV disease. Median follow-up was 58 months. 9 of 94 DLBCL samples (9.6%) were positive for CD30 by immunohistochemistry. By Kaplan-Meier analysis, the CD30-positive cases showed a decreased overall survival compared to the CD30-negative cases (Figure 1, p=0.044). Multivariate analysis using a Cox proportional hazard model confirmed that CD30 expression was independent of IPI and a significant factor for overall survival (hazard ratio = 3.05; 95% confidence interval = 1.12-8.30; p = 0.0291). All 9 of the CD30-positive DLBCL samples were of the non-germinal center B-cell-like (NGC) subtype using the Hans immunohistochemical algorithm, which was significantly more than the CD30-negative samples (42/85) (p = 0.003). Conclusion CD30 expression was associated with poor prognosis in our cohort, in contrast to recent studies. However, CD30 expression was highly associated with the NGC subtype of DLBCL and might contribute to the pathogenesis of these lymphomas through NF-κB activation. Given the poor prognosis of NGC DLBCLs, targeting CD30 in DLBCL should be explored. Disclosures: No relevant conflicts of interest to declare.

Effect of addition of rituximab to CHOP on survival of patients in both the GCB and non-GCB subgroups of diffuse large B-cell lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8040-8040 ◽  
Author(s):  
K. Fu ◽  
K. D. Perry ◽  
L. M. Smith ◽  
C. P. Hans ◽  
T. C. Greiner ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Rank Test ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

8040 Background: Diffuse large B-cell lymphoma (DLBCL) includes at least two prognostically important subgroups, i.e. germinal center B-cell (GCB) and activated B-cell (ABC) DLBCL, which were initially characterized by gene expression profiling and subsequently validated by immunostaining. Bcl-2 has also been identified as a prognostic indicator in the ABC subgroup. However, with the addition of rituximab (R) to standard chemotherapy, the prognostic significance of this subclassification of DLBCL is unclear. Methods: We studied 119 cases of de novo DLBCL including 70 cases treated with R-CHOP and 49 cases treated with CHOP. The cases were assigned to either the GCB or non-GCB subgroups using the methodology described by Hans et al (Blood 2004; 103:275). Characteristics of the patients were compared using the Chi-square test. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan Meier method and compared with the log-rank test. Results: The median age of the 119 patients was 67 years, ranging from 20 to 90 years, and there were 62 males and 57 females. The clinical characteristics of patients treated with CHOP versus R-CHOP, including the IPI, were comparable. R-CHOP was more effective than CHOP with improved 5-year EFS (63% vs 41%, p=0.013) and OS (78% vs 47%, p<0.001). In both patient groups treated with R-CHOP or CHOP, the GCB subgroup had a significantly better 5-year EFS and OS compared to the non-GCB subgroup (OS: 91% vs 64% for R-CHOP, p=0.0073; 67% vs 31% for CHOP, p=0.034, respectively). Additionally, both the GCB and non-GCB subgroups treated with R-CHOP had a significantly improved OS compared to their respective subgroups receiving CHOP alone (GCB, p=0.015; non-GCB, p=0.019). Bcl-2 expression was not a significant predictor in either the GCB or non-GCB subgroups treated with R-CHOP (OS, GCB: p=0.32; non-GCB: p=0.43). Conclusions: In this retrospective study, we demonstrate that subclassification based on the cell of origin continues to have prognostic significance in patients with DLBCL treated with R-CHOP. Addition of rituximab to CHOP improves the overall survival of patients with DLBCL in both the GCB and non-GCB subgroups. No significant financial relationships to disclose.

CD19-Negative Diffuse Large B-Cell Lymphoma Shows High Serum LDH Level and Poor Prognosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1924-1924 ◽  
Author(s):  
Miho Kimura ◽  
Motoko Yamaguchi ◽  
Satoshi Ueno ◽  
Shoko Ogawa ◽  
Kana Miyazaki ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Clinical Features ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Serum ◽  
Large B Cell Lymphoma ◽  
Cd19 Expression ◽  
Large B Cell

Abstract CD19 is one of the most representative B-cell markers, and is widely used in diagnostic immunophenotyping in diffuse large B-cell lymphoma (DLBCL). However, it is known that the frequency of CD19 expression in DLBCL is less than that of CD20, and the clinical significance of CD19 expression has not yet been thoroughly examined. To clarify the clinical behavior of CD19-negative (CD19−) DLBCL, we have compared the clinical features, immunophenotype, and prognosis in relation to CD19 expression. The diagnosis of DLBCL was made according to the WHO Classification. We examined CD19 expression by means of immunohistochemistry using frozen sections with a monoclonal antibody, Leu12 (Becton Dickinson). Between 1987 and 2002, 227 cases of de novo DLBCL were examined the expression of CD19 in our laboratory. Anthracycline-containing chemotherapies were selected as the first-line treatment in 192 cases (85%). None was treated with rituximab. CD19 was expressed in 205 cases (90%), and 226 cases (99%) were positive for CD20. In 22 cases of CD19-negative (CD19−) DLBCL, the median age was 63 (39–79), and the male/female ratio was 11/11. According to CD19 expression, our DLBCL cases showed the following clinical features: male/female (CD19+ DLBCL 111/94, CD19− DLBCL 11/11: NS), age>60 (70%, 55%: NS), PS>1 (20%, 36%: P=0.07), sLDH>1xN (44%, 73%: P=0.01), extranodal involvement>1 site (12%, 18%: NS), stage III/IV (41%, 54%: NS), B symptom present (29%, 45%: NS). CD19− DLBCL expressed BCL2 protein less frequently than CD19+ DLBCL (P=0.03). The expression of CD5, CD10, CD21, BCL6, and MUM1 did not show a significant difference between CD19+ DLBCL and CD19− DLBCL. CD19− DLBCL showed significantly worse survival than CD19+ DLBCL (P=0.04, log-rank test). These findings suggest that the loss of CD19 expression in DLBCL is associated with high serum LDH level and poor prognosis. Simultaneous examination of CD19 and CD20 in diagnosis of DLBCL is recommended. Overall survival for patients with CD19+ DLBCL and with CD19− DLBCL. Overall survival for patients with CD19+ DLBCL and with CD19− DLBCL.

Prognostic Significance of Cell of Origin Subclassification in Diffuse Large B Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5081-5081
Author(s):  
Muath Dawod ◽  
Juan Gomez-Gelvez ◽  
Ahmad Mattour ◽  
Kedar V. Inamdar ◽  
Nalini Janakiraman
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Free Survival ◽  
Large B Cell Lymphoma

Abstract Abstract 5081 Background: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that has been divided into three different prognostic subgroups: Germinal Center B cell-like (GC), Activated B cell-like (ABC) and type 3 according to gene expression profile using cDNA. Immunohistochemistry (IHC) has been used as surrogate to identify these cell-of-origin subgroups. Data about the prognostic value of IHC has been conflicting. Patients and methods: In this retrospective study, we reviewed the charts of 252 patients diagnosed with DLBCL at Henry Ford Hospital from 1999 to 2012. We excluded patients with HIV, transformed lymphomas and unavailable samples. Data was collected on a total of 157 patients. The following data was gathered: age, sex, race, IPI score, disease stage, hemoglobin, white blood and platelet counts, best response achieved and dates of treatment start, relapse, death or last follow up. Tissue microarray slides with the following IHC stains (CD10, MUM1, Bcl6) were prepared and reviewed when needed. Using Hans Algorithm, samples were divided into two major groups (GC-like and non-GC-like). 3-year progression free and overall survivals were compared between all subgroups using a log-rank test. Continuous variables were reported as median and range, and compared using Wilcoxon rank-sum tests. Categorical variables were reported as median and range, and compared using Chi-square tests. Statistical significance was set at p<0. 05. Results: Eighty patients (51%) were classified as GC-like, and 77 patients (49%) as non-GC-like. GC-like subgroup had a significantly longer 3-year progression free survival (90% vs 74%, P=0. 024), as compared with the non-GC-like subgroup. There was a trend toward longer overall survival but it didn't reach statistical significance (74% vs 67%, P=0. 161). For all patients, IPI stands as a strong prognostic index with 3-year overall survival of (85% and 46%, P=<. 001) in patients with low IPI (0 to 2) and high IPI (3 to 5) respectively. Interestingly, in patients with low IPI, cell of origin stands as a prognostic factor with 3-year progression free survival of (96% and 81%, P=0. 032) in GC-like and non-GC-like groups respectively. While in patients with high IPI, there was no significant difference in progression free survival in cell-of-origin subgroups. Conclusion: Cell of origin subclassification as determined by IHC surrogate markers predict for better progression free survival in GC-like subgroup but not for overall survival. While this prognostic value was maintained in patients with low IPI, there was no prognostic significance in patients with high IPI. IPI is still a valuable prognostic tool in patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunophenotypic characteristics of Diffuse Large Bcell Lymphoma

2021 ◽  
Vol 8 (1) ◽  
pp. 1049-1052
Author(s):  
SM Mahbubul Alam ◽  
Ahmed Khaled
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Molecular Subtype ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Wide Range ◽  
Large B Cell

Introduction: Immunohistochemistry (IHC) is essential in the diagnostic workup of Diffuse Large B cell lymphoma (DLBCL). Determination of biological heterogenicity of Diffuse Large B-cell Lymphoma (DLBCL) is critical to institute precise treatment and predict prognosis. IHC confirms B cell phenotypes, reflects molecular subtype based on cell of origin and determines other immunophenotypic characteristics. Methods and Material: All cases of DLBCL diagnosed in 2020 (Jan-Dec) in histopathology department of Evercare Hospital Dhaka were included in this study. Histopathological sections were stained with CD20, CD3, CD5, CD30, BCL2, BCL6, CD10, MUM1, MYC, Ki67 and other markers. Hans algorithm was applied to classify DLBCL cases into germinal center B-cell (GCB) or Non-GCB. Results: Out of 64 DLBCL cases, 21 (24%) of DLBCL were GCB, while 76% (43 cases) were non-GCB subtypes. 30% cases of DLBCL showed double expression for MYC and BCL2. Fewer cases were immunoreactive for CD5 and CD30. Conclusion: This first study at Dhaka with wide range of antibody to characterize the Immunophenotypic features of DLBCL. The main finding of this study is the identification of non-germinal center B-cell (non-GCB) as the major immunophenotype of DLBCL. This may be an enabler for further studies to observe the clinical outcome of different subtypes of GCB and Non-GCB. Bioresearch Commu. 8(1): 1049-1052, 2022 (January)

scholarly journals Clinicopathologic Characteristics and Genomic Profiling of De Novo CD5 Positive Diffuse Large B-Cell Lymphoma: A Multicenter Retrospective Study in China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4568-4568
Author(s):  
Wei Sang ◽  
Yuhan Ma ◽  
Xiangmin Wang ◽  
Ziyuan Shen ◽  
Linyan Xu ◽  
...  
Keyword(s):  
B Cell ◽  
Poor Prognosis ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Genomic Profiling ◽  
Cns Involvement ◽  
Clinicopathologic Characteristics ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract De novo CD5 positive diffuse large B cell lymphoma (CD5+ DLBCL) has poor survival in the era of immunochemotherapy. We conducted a multi-center retrospective study to explore the clinicopathologic characteristics, genomic profiling and prognostic elements of 61 CD5+ DLBCL and 60 CD5- DLBCL patients in China. In contrast with CD5- DLBCL, elderly onset, advanced stage, central nervous system (CNS) involvement, as well as MYC/BCL-2 and P53 overexpression were more prevalent in CD5+ DLBCL. In addition, most of CD5+ DLBCL patients were of non-germinal center B-cell-like (non-GCB) and activated B-cell-like (ABC) subtype according to immunohistochemistry and Lymph2Cx assay. Genetic analysis by next generation sequencing (NGS) showed the proportion of MCD subtype in CD5+ DLBCL was higher than that of CD5- DLBCL (50% vs 5%, p = 0.0007). Compared with CD5- cohort, CD5+ DLBCL patients showed poorer 5-year overall survival (OS) (70.9% vs 39.0%, p&lt;0.001), independent of cell-of-origin and MYC/BCL-2, P53 and BCL-6 status. Multivariate analysis showed that age &gt;76 years, advanced stage, CNS involvement and hypoalbuminemia were independent factors associated with poor prognosis in CD5+ DLBCL. In conclusion, CD5+ DLBCL conveyed poor prognosis and showed distinctive clinicopathologic characteristics and predominant genetic features of ABC and MCD subtypes. Disclosures No relevant conflicts of interest to declare.

scholarly journals Upregulation of CD47 Expression in De Novo Diffuse Large B-Cell Lymphoma Is More Frequent in Activated B-Cell Type

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3507-3507
Author(s):  
Winston Y Lee ◽  
Anamarija M. Perry ◽  
Vero Azcutia ◽  
Alex F. Herrera ◽  
Pamela Skrabek ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Research Funding ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Surface Receptor ◽  
Large B Cell Lymphoma ◽  
Frequent Mutations ◽  
Large B Cell

Abstract CD47 is a marker of self that provides a "don't-eat-me-signal" through activation of signal-regulatory protein alpha (SIRPa), a cell surface receptor expressed on monocytes/macrophages and granulocytes. This interaction negatively regulates effector functions such as, phagocytosis, migration, and superoxide production. Upregulation of CD47 expression in cancer, including diffuse large B-cell lymphoma (DLBCL), has emerged as a mechanism to escape innate immune surveillance. Using conventional immunohistochemical detection, we assessed CD47 expression in DLBCL and interrogated its association with clinicopathologic features. Patients with de novo DLBCL were identified from two large institutions and were uniformly treated with R-CHOP and had sufficient material for study. Immunohistochemical stains (IHC) were performed on FFPE tissue (Hans algorithm, BCL2, MYC, and CD47) and scored semi-quantitatively from no reactivity (0) to strong (2 and 3; Figure 1). Mutational analysis using a 334 gene target sequencing panel, gene expression profiling using Lymph2Cx to determine the cell of origin (COO), and FISH analysis for MYC, BCL2, and BCL6 translocations, were performed. The Lymphgen tool (Wright et al, 2020) was also used to determine the DLBCL group. Fisher's exact test and Kaplan-Meier survival analysis for overall survival (OS) were performed and P &lt;0.05 was considered significant. CD47 expression was assessed by IHC in a cohort of 152 cases of de novo DLBCL, including 107 cases of germinal center B-cell (GCB) type (70%), 37 cases of activated B-cell (ABC) type (24%), and 8 cases of intermediate type (5%). A total of 17 cases (11%) showed strong and diffuse CD47 expression with IHC scores of 2 or above (CD47hi). CD47hi cases were significantly more frequent in ABC DLBCL (24%, 9/37) than GCB DLBCL (6%, 6/107; P=0.003). The remaining 2 CD47hi cases were in the intermediate DLBCL group (25%, 2/8). ABC DLBCL with CD47hi showed more frequent mutations with TET2 (33% vs 7%; P=0.08) and ZFP36L1 (22% vs 0%; P=0.05) compared to cases with low expression of CD47 with IHC scores of less than 2 (CD47low). ABC DLBCL with CD47low showed more frequent mutations of NOTCH2 (18% vs 0%; P=0.31) and MYD88 (29% vs 11%; P=0.4) compared to CD47hi. GCB DLBCL with CD47hi showed frequent mutations of TP53 (67% vs 21%; P=0.026) and CCND1 (33% vs 0%; P=0.003) compared to CD47low. None of the 13 cases with double- or triple-hit for MYC, BCL2 and/or BCL6 showed CD47 expression. The Lymphgen tool showed that cases of DLBCL with CD47hi were mostly in the 'other' group (50%), with other groups represented such as ST2 (21%), EZB (14%), MCD and BN2 (1 case each). There was no difference in overall survival (OS) between CD47hi and CD47low DLBCL (5-year OS, 75% vs 72%; P=0.57), or with the GCB or ABC subtypes. Strong expression with CD47 is more frequent in ABC DLBCL and is seen in a subset of GCB DLBCL with mutations in TP53 and/or CCND1. The level of CD47 expression does not appear to predict OS in patients with DLBCL treated with R-CHOP. This study demonstrates that conventional immunohistochemical methods can readily identify DLBCL with high CD47 expression, and these patients may benefit from the use of anti-CD47 therapy. Figure 1 Figure 1. Disclosures Herrera: Gilead Sciences: Research Funding; Takeda: Consultancy; Tubulis: Consultancy; Karyopharm: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Seagen: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Kite, a Gilead Company: Research Funding.

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