scholarly journals Nfatc1 and Tumor Associated Macrophages Affect Progression of Certain Subsets of Diffuse Large B Cell Lymphoma Non-Gcb Subtypes

2021 ◽  
Vol 5 (2) ◽  
pp. 345-353
Author(s):  
Krisna Murti ◽  
Muslina Muslina ◽  
Ika Kartika ◽  
Rachmat Hidayat ◽  
Ella Amalia
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Therapeutic Strategies ◽  
Proliferation Index ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Positive Expression ◽  
Activated T Cell ◽  
Large B Cell

A B S T R A C TIntroduction Diffuse large B cell lymphoma (DLBCL) is the most common type ofnon-Hodgkin lymphoma among B cell lymphomas. The interaction of tumor cellswith their microenvironment (tumor microenvironment, TME) leads to progressivityof malignancy. CD163 + macrophages known as components of TME. Nuclear factorof activated T cell (NFATc1) and MYC are important transcription factors inmalignant transformation and progression. Therapeutic strategies were fastdeveloped, nevertheless, efforts to decrease DLBCL morbidity and mortality areunsatisfied, therefore,new markers for prognosis and or therapeutic options of thepatients are necessary. This study was aimed to investigate NFATc1 expression inDLBCL and its TME. Methods: Thirty-two paraffin blocks were selected thenimmunostained for expression of NFATc1, MYC, and CD163. Clinopathologic datai.e. ages, gender, and proliferation index Ki-67 were obtained. Data was analyzedby statistics Result: Positive expression of CD163 and NFATc1 was among 55%and 45% of cases respectively. All DLBCL cases in this study were non-GCBsubtype and more patients were under 60 years (66%). Positive expression ofCD163 was higher in males (69%) and in patients under 60 years (63%). Tissuespositive for both NFATc1 and CD163 was observed higher among males andpatients under 60 years. Conclusion: NFATc1 may affect development and orprogression of certain subsets of DLBCL non-GCB subtype.

scholarly journals NFATc1 and Tumor Associated Macrophages Affect Progression of Certain Subsets of Diffuse Large B Cell Lymphoma Non-GCB Subtypes

2021 ◽  
Vol 5 (3) ◽  
pp. 320-328
Author(s):  
Krisna Murti ◽  
Muslina Muslina ◽  
Ika Kartika ◽  
Rachmat Hidayat ◽  
Ella Amalia
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Proliferation Index ◽  
Ki 67 ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Positive Expression ◽  
Activated T Cell ◽  
Large B Cell

Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma among B cell lymphomas. The interaction of tumor cells with their microenvironment (tumor microenvironment, TME) leads to progressivity of malignancy. CD163 + macrophages known as components of TME. Nuclear factor of activated T cell (NFATc1) and MYC are important transcription factors in malignant transformation and progression. Therapeutic strategies were fast developed, nevertheless, efforts to decrease DLBCL morbidity and mortality are unsatisfied, therefore,new markers for prognosis and or therapeutic options of the patients are necessary. This study was aimed to investigate NFATc1 expression in DLBCL and its TME. Methods: Thirty-two paraffin blocks were selected then immunostained for expression of NFATc1, MYC, and CD163. Clinopathologic data i.e. ages, gender, and proliferation index Ki-67 were obtained. Data was analyzed by statistics Result: Positive expression of CD163 and NFATc1 was among 55% and 45% of cases respectively. All DLBCL cases in this study were non-GCB subtype and more patients were under 60 years (66%). Positive expression of CD163 was higher in males (69%) and in patients under 60 years (63%). Tissues positive for both NFATc1 and CD163 was observed higher among males and patients under 60 years. Conclusion: NFATc1 may affect development and or progression of certain subsets of DLBCL non-GCB subtype.

scholarly journals Immunophenotypic Analysis of AIDS-Related Diffuse Large B-Cell Lymphoma and Clinical Implications in Patients From AIDS Malignancies Consortium Clinical Trials 010 and 034

2009 ◽  
Vol 27 (30) ◽  
pp. 5039-5048 ◽  
Author(s):  
Amy Chadburn ◽  
April Chiu ◽  
Jeannette Y. Lee ◽  
Xia Chen ◽  
Elizabeth Hyjek ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hiv Infection ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response To Therapy ◽  
Proliferation Index ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose Diffuse large B-cell lymphoma (DLBCL) represents a clinically heterogeneous disease. Models based on immunohistochemistry predict clinical outcome. These include subdivision into germinal center (GC) versus non-GC subtypes; proliferation index (measured by expression of Ki-67), and expression of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We sought to determine whether immunohistochemical analyses of biopsies from patients with DLBCL having HIV infection are similarly relevant for prognosis. Patients and Methods We examined 81 DLBCLs from patients with AIDS in AMC010 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP-rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose-adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials and compared the immunophenotype with survival data, Epstein-Barr virus (EBV) positivity, and CD4 counts. Results The GC and non-GC subtypes of DLBCL did not differ significantly with respect to overall survival or CD4 count at cancer presentation. EBV could be found in both subtypes of DLBCL, although less frequently in the GC subtype, and did not affect survival. Expression of FOXP1, Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS-related DLBCL. Conclusion These data indicate that with current treatment strategies for lymphoma and control of HIV infection, commonly used immunohistochemical markers may not be clinically relevant in HIV-infected patients with DLBCL. The only predictive immunohistochemical marker was found to be Ki-67, where a higher proliferation index was associated with better survival, suggesting a better response to therapy in patients whose tumors had higher proliferation rates.

PP-028 INVESTIGATION ON THE FREQUENCY OF CD10, CD30, BCL-2, BCL-6, MUM-1, P53, KI-67 AND IMPACT TO THE PROGNOSIS IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA

2014 ◽  
Vol 38 ◽  
pp. S36
Author(s):  
P. Haciboncuk ◽  
M. Yilmaz ◽  
G. Soylu ◽  
E. Gundogan ◽  
D. Yanardag Acık ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals C-MYC Protein Expression and High Ki-67 Proliferative Index are Predictives of Disease Relapse in Diffuse Large B Cell Lymphoma

2021 ◽  
Vol 6 (1) ◽  
pp. 15-20
Author(s):  
Mahmoud Tag El-Hussien ◽  
Nadia Mokhtar ◽  
Eman Naguib Khorshed
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Statistical Prediction ◽  
Proliferative Index ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Objective: To evaluate the status of C-MYC protein expression and Ki-67 proliferative index and to clarify their role in predicting relapse of diffuse large B cell lymphoma (DLBL). Materials and Methods: A retrospective study conducted on 50 cases diagnosed as DLBL in a 3 years’ time period from January 2014 till December 2016, collected from the archive of Pathology Departments of the National Cancer Institute Cairo - Egypt, Misr University for Science and Technology and private labs of authors. The diagnosis of DLBL for all cases, both nodal and extranodal, was confirmed by histopathologic examination and immunophenotyping. Automated immunohistochemical staining using antibodies against C-MYC protein and MIB-1 was used to evaluate the C-MYC expression in tumor cells and to assess their proliferative ability by calculating Ki-67 labelling index. The relation between the percentage of C-MYC protein expression, Ki-67 proliferative index, clinical data and the relapse status during the follow up period were analyzed. Results: A total of 50 cases of DLBL in both nodal and extra-nodal sites were included. Twenty-three cases (46%) were expressing the C-MYC protein, and 29 cases (58%) showed high Ki-67 proliferative index. Twenty-two cases (44%) relapsed during the follow-up period. Positive C-MYC protein expression was significantly associated with high Ki-67 proliferative index. C-MYC protein expression and high Ki-67 proliferative index were independently associated with disease relapses in 81.8% and 86.4% of cases respectively. Cases with combined C-MYC protein expression and high Ki-67 proliferative index showed statistical prediction of relapse in 81.8% of cases. Conclusion: C-MYC protein expression and high Ki-67 proliferative index were independently associated with relapse of diffuse large B cell lymphoma. Furthermore, the combined positive C-MYC protein expression and high Ki-67 proliferative index is better than a single positive test in predicting relapses among DLBL patients.

scholarly journals Prognostic significance evaluation of B-cell lymphoma 2 (BCL2) and Ki-67 expression in diffuse large B-cell lymphoma patients

2019 ◽  
Vol 6 (1) ◽  
pp. e07-e07
Author(s):  
Hossein Rahimi ◽  
Zahra Rezaei Borojerdi ◽  
Sajad Ataei Azimi ◽  
Elnaz Rashidian ◽  
Amirhossein Jafarian
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Molecular Heterogeneity ◽  
Clinical Genetic ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Bcl2 Expression

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphatic neoplasm, accounting for about 30–40% of non-Hodgkin’s lymphoma cases. Objectives: DLBCL is a progressive disease with clinical, genetic and molecular heterogeneity. The prognostic value of B-cell lymphoma 2 (BCL2) and Ki-67 in DLBCL patients has been controversial. Patients and Methods: In this study, we investigated the correlation of BCL2 and Ki-67 expression with clinical features such as age, gender, B symptoms and lactate dehydrogenase (LDH) levels, subtypes of DLBCL, its staging and prognosis in 36 cases of DLBCL. The expression of BCL2 and Ki-67 was measured by immunohistochemistry. Results: There was no significant correlation between BCL2 expression and staging (P=0.082), however Ki-67 expression had a significant correlation with staging (P=0.002). There was no statistically significant correlation between BCL2 and Ki-67 with prognosis of the disease. We found a significant correlation between the germinal center B-cell (GCB) and non- GCB subtypes with BCL2 expression (P=0.024), since patients with non- GCB subtype had a higher BCL2 expression. Our study also demonstrated a significant relationship between BCL2 and Ki-67 expression, therefore, with the increase of the expression of a marker, another increases (P=0.045). Conclusion: BCL2 and Ki-67 expressions were not associated with prognosis. Overexpression of Ki-67 was associated with higher clinical stages. BCL2 expression is higher in non-GCB subtype of DLBCL. Therefore, our study shows that the subsequent studies of BCL2 and other biomarkers in the DLBCL should be based on the DLBCL subtypes.

Low rather than high Ki-67 protein expression is an adverse prognostic factor in diffuse large B-cell lymphoma

2008 ◽  
Vol 49 (8) ◽  
pp. 1501-1509 ◽  
Author(s):  
Sverker Hasselblom ◽  
Börje Ridell ◽  
Margret Sigurdardottir ◽  
Ulrika Hansson ◽  
Herman Nilsson-Ehle ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Ki 67 ◽  
Adverse Prognostic Factor ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals A rare case of primary pulmonary diffuse large B cell lymphoma with CD5 positive expression

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 49-51 ◽  
Author(s):  
Tao Wang ◽  
Mingming Zhang ◽  
Jianrong Sun ◽  
Dong Hao ◽  
Zhijiang Qi ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Symptoms ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Imaging Features ◽  
Ct Guided ◽  
Large B Cell Lymphoma ◽  
Halo Sign ◽  
Positive Expression ◽  
Large B Cell

AbstractPrimary pulmonary diffuse large B-cell lymphoma (PPDLBCL) is extremely rare. Its clinical symptoms and signs are nonspe cific, and imaging features also have not yet been well-defined. Further description is important for the diagnosis and treatment of PPDLBCL. Herein, we reported a case of a patient who suffered from bilateral chest pain and dyspnea. Computed tomography (CT) of chest demonstrated bilateral lung mass, consolidations and reverse halo sign, while consolidations and reverse halo sign are uncommon according to previous reports. Tissue samples were taken by CT guided needle biopsy. The histological samples showed PPDLBCL. This case was special in view of positive expression of CD5. After the case was treated by cyclophosphamide pirarubicin vindesine dexamethasone (CHOP) chemotherapy for six courses, her clinical symptoms were partially alleviated, while CT showed progression disease. This case report highlights different imaging features and characteristics of molecular biology, and reviews study progress of PPDLBCL.

The Grey Zone between Burkitt and Diffuse Large B Cell Lymphomas: Impact of Chromosomal Breakponts at Myc and Other Loci.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2275-2275
Author(s):  
Eugenia Haralambieva ◽  
Evert-jan Boerma ◽  
Gustaaf van Imhoff ◽  
Stefano Rosati ◽  
Ed Schuuring ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Grey Zone ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Consensus Diagnosis ◽  
Phenotypic Shift ◽  
Large B Cell

Abstract A prompt distinction of Burkitt lymphoma (BL) versus diffuse large B cell lymphoma (DLBCL) has important clinical implications. We analyzed 74 adult grey zone lymphomas (BL/DLBCL) and 10 reference pediatric BL using immunohistochemistry for Ki-67, CD10, bcl2 and bcl6, and Fluorescence In Situ Hybridization (FISH) for MYC, BCL2 and BCL6 breakpoints. Four hematopathologists reached a final (consensus) diagnosis independently in 80% of the reference BL, 24% of the test BL and 69% of the DLBCL. A MYC breakpoint was detected in all reference BL, 95% of the test BL and 35% of the DLBCL. BCL2 and BCL6 breakpoints were infrequent in BL (5 and 6%) and DLBCL (13% and 16%). Three BL and 5 DLBCL contained double breakpoints. A phenotypic shift to BL in the DLBCL group was indicated by the expression of CD10 and bcl6 in 67% and 91% of the cases, respectively. One third of all lymphomas showed a classical genotype and expression pattern of BL (MYC breakpoint+, Ki-67>90%, CD10+, bcl6+, bcl2-) but only 63% of these cases were classified as BL. Our data indicate that a subgroup of DLBCL shares markers with BL, which is probably due to an overlapping histogenesis of both tumors. Value of immunohistochemistry and additional FISH for BCL2 and BCL6 breakpoints to reach the consensus diagnosis in 38 MYC breakpoint carrying cases of adult grey zone BL / DLBCL lymphomas BCL2 and BCL6 breakpoint no restriction not present no restriction not present 38 / 74 cases carried a MYC/8q24 breakpoint phenotype no restriction no restriction Ki67>90%, CD10+, bcl6+, bcl2- Ki67>90%, CD10+, bcl6+, bcl2- N 38 30 24 22 Burkitt (%) 20 (53) 17 (57) 15 (63) 15 (68) DLBCL (%) 18 (47) 13 (43) 9 (37) 7 (32)

HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1642-1642
Author(s):  
Dorota Jesionek-Kupnicka ◽  
Marcin Bojo ◽  
Monika Prochorec-Sobieszek ◽  
Anna Szumera-Cieckiewicz ◽  
Joanna Jablonska ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Clinical Course ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Class Ii ◽  
Hla Class Ii ◽  
Large B Cell Lymphoma ◽  
Positive Expression ◽  
Large B Cell

Abstract Major histocompatibility complex (MHC) class I and class II are similar in function since they present peptides at the cell surface to CD8+ and CD4+ T cells, respectively. There is mounting evidence indicating that MHC genes play a role in the etiology and clinical course of non-Hodgkin lymphomas (NHL), especially in diffuse large B-cell lymphoma (DLBCL). We investigated the expression of human leukocyte antigen-G (HLA-G) and HLA class II protein in DLBCL among 148 patients and related their expression to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (P= 0.04). There was no impact of HLA-G or HLA class II expression on the probability of progression-free survival (PFS). Patients with positive HLA-G expression presented a trend towards a higher 3-year overall survival (OS) rate compared to those with negative expression of HLA-G (P= 0.08). The estimated 3-year OS rate of patients with positive HLA class II expression was 59.4% (95%CI 49-69) in comparison to the 37.4% (95%CI 22-56; P= 0.04) in subjects with negative expression. In a multivariate Cox analysis adjusted for the IPI factors, we found that both the intermediate high/high IPI risk group (P= 0.001) and the loss of HLA class II expression (P= 0.05) independently increased the risk of death in the study group. We also investigated whether the impact of HLA class II expression on OS may be related to the subtypes of DLBCL. In the subgroup of 58 patients (39%) with GCB-type pattern, the patients with the loss of HLA class II expression presented a significantly lower 3-year OS rate than those with its positive expression (26% [95% CI 10-53] vs 68.2% [95% CI 51-81], P= 0.02). In contrast, in the subgroup of 90 non-GCB patients (61%), HLA class II expression did not influence OS. To further explore the unexpected favorable effect of positive HLA-G expression on the clinical course of DLBCL, we performed an additional analysis that considered the type of treatment (chemotherapy with or without rituximab). In the group of patients treated with immunochemotherapy, a more pronounced effect of the positive HLA-G expression on OS was revealed. The estimated 3-year OS rate of patients with the positive HLA-G expression was 73.3 % (95% CI 49-88) compared to 47.5% (95% CI 35-60, P= 0.03) in subjects with the negative HLA-G expression. In contrast, in the group treated with CHOP-like regimens, no significant impact of HLA-G expression on OS was observed: the 3-year OS rate for HLA-G positivity was 20% (95% CI 4-62) vs 55.3% (95% CI 37-72; P= 0.08) for the absence of HLA-G. Additionally, the prognostic value of HLA class II expression was also shown to depend on the use of rituximab as a part of first line treatment. In the patients receiving immunochemotherapy, those that had positive HLA class II expression demonstrated a 3-year OS rate of 65.3% (95% CI 52-76) compared to 29.6% (95% CI 13-53, P= 0.04) in subjects with the loss of HLA class II expression. However, HLA class II expression did not have a prognostic impact on OS in the patients treated with chemotherapy alone: the 3-year OS rate was 49.5% (95% CI 32- 67) in the subjects with positive expression in comparison to 50% (95% CI 15-85, P= 0.8) in those with the loss of HLA class II expression. In conclusion, we demonstrated for the first time expression of HLA-G protein in DLBCL and its association with the clinical course of the disease as well as we confirming the association of the loss of HLA class II protein expression with poor survival in patients treated with immunochemotherapy. Although the clinical significance of the loss of HLA class II protein expression seems to be well understood, the contribution of HLA-G to the prognosis of B-cell malignancies deserves further study, especially its immunoregulatory functions in relation to treatment with rituximab, which remains an open question. Disclosures Robak: MorphoSys AG: Research Funding.

High Ki-67 expression in involved bone marrow predicts worse clinical outcome in diffuse large B cell lymphoma patients treated with R-CHOP therapy

2014 ◽  
Vol 101 (2) ◽  
pp. 140-147 ◽  
Author(s):  
Moo-Kon Song ◽  
Joo-Seop Chung ◽  
Je-Jung Lee ◽  
Deok-Hwan Yang ◽  
In-Suk Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Outcome ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Chop Therapy
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