Prevalence and Prognostic Molecular Profiles in Hepatitis B Virus Infected Patients with Diffuse Large B Cell Lymphoma: A Retrospective Study From Chinese Population

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5211-5211
Author(s):  
Huijie Wang ◽  
Junning Cao ◽  
Xiaonan Hong

Abstract Abstract 5211 Introduction: Meta-analysis demonstrated that B cell lymphoma appears to be at high risk of infection by Hepatitis B Virus (HBV). Recently, cohort study showed HBV infection is associated with the increasing risk of B cell type lymphoma. Retrospective studies demonstrated high prevalence of HBV infection in Chinese lymphoma patients, with HBsAg-positive rates ranging from 23.5% to 30.5%. HBsAg-positive Diffuse Large B Cell Lymphoma (DLBCL) patients are associated with younger age and more advanced stage. However, the relation between HBV infection and poor prognosis in DLBCL remains uncertain. Molecular markers based on Immunohistochemical (IHC) expression were widely used as prognostic markers in DLBCL. Our study aimed to investigate the prevalence of HBVinfection in the different subtypes of lymphoma, and the molecular prognostic profiles in HBsAg-positive DLBCL. Patient and Methods: From Jan 2008 to Dec 2010, a total of 672 patients diagnosed as lymphoma were tested for HBsAg. Of these, 399 were male and 273 were female; 426 were B-NHL, 216 were T-NHL and 30 were HL. The expressions of BCL-2, BCL-6, CD10, MUM-1 were tested in patients diagnosed with DLBCL. Results: We found the overall HBsAg-positive rate was 15.9% (107/672) in total lymphoma patients. The positive rate of HBsAg was higher in B-NHL patients (20%,85/426) than T-NHL(9.7%,21/216) and HL (3.3%,1/30) (P<0.001).The lower prevalence were observed several subtypes of lymphoma including mantle cell lymphoma (0/20, 0%), Burkett's lymphoma (0/13, 0%), HL (1/29, 3.3%) and PTCL (4/53, 7.5%).The rate of HBV infection was higher in DLBCL patients (20.9%, 68/326). Among prognostic molecular profiles in DLBCL, the positive expression rates of BCL-2, BCL-6, CD10 and MUM-1 were 65.4% (134/205), 51.3% (116/226), 17% (39/230) and 61.5% (139/226), respectively. The non-GCB subtype accounted of 68.7% of DLBCL. Between HBsAg negative and positive group of DLBCL, the positive expression rates of BCL-2 were 64.1% vs 69.2% (P=0.498), CD 10 were 16.6% v 18.2%(P=0.781), MUM-1 were 60.5% vs 64.8%(P=0.567). However, the BCL-6 positive rate was slight higher in HBsAg negative group compared with positive group (55% vs40%, P=0.053). Finally, non-GCB subtype rates were 67.7% vs 68.7% in HBsAg negative and positive group DLBCL. Conclusion: Our date demonstrated that the infection rate of HBV was higher in DLBCL, whereas lower in the subtypes of mantle cell lymphoma, burkitt's lymphoma and HL. Based on IHC analysis, non-GCB subtype accounted of two-third of DLBCL in our series. Patients with HBsAg-positive DLBCL had lower positive rate of BCL-6. However, the expression of Bcl-2, CD10, MUM-1 seems no significant difference between patients with HBsAg-positive and negative DLBCL. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2018 ◽  
Vol 131 (24) ◽  
pp. 2670-2681 ◽  
Author(s):  
Weicheng Ren ◽  
Xiaofei Ye ◽  
Hong Su ◽  
Wei Li ◽  
Dongbing Liu ◽  
...  

Hepatitis B virus (HBV) infection is endemic in some parts of Asia, Africa, and South America and remains to be a significant public health problem in these areas. It is known as a leading risk factor for the development of hepatocellular carcinoma, but epidemiological studies have also shown that the infection may increase the incidence of several types of B-cell lymphoma. Here, by characterizing altogether 275 Chinese diffuse large B-cell lymphoma (DLBCL) patients, we showed that patients with concomitant HBV infection (surface antigen positive [HBsAg+]) are characterized by a younger age, a more advanced disease stage at diagnosis, and reduced overall survival. Furthermore, by whole-genome/exome sequencing of 96 tumors and the respective peripheral blood samples and targeted sequencing of 179 tumors from these patients, we observed an enhanced rate of mutagenesis and a distinct set of mutation targets in HBsAg+ DLBCL genomes, which could be partially explained by the activities of APOBEC and activation-induced cytidine deaminase. By transcriptome analysis, we further showed that the HBV-associated gene expression signature is contributed by the enrichment of genes regulated by BCL6, FOXO1, and ZFP36L1. Finally, by analysis of immunoglobulin heavy chain gene sequences, we showed that an antigen-independent mechanism, rather than a chronic antigenic simulation model, is favored in HBV-related lymphomagenesis. Taken together, we present the first comprehensive genomic and transcriptomic study that suggests a link between HBV infection and B-cell malignancy. The genetic alterations identified in this study may also provide opportunities for development of novel therapeutic strategies.


2020 ◽  
Author(s):  
Shunfeng Hu ◽  
Na Chen ◽  
Kang Lu ◽  
Changqing Zhen ◽  
Xiaohui Sui ◽  
...  

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) has been correlated with virus infection and immunity status. Hepatitis B virus (HBV) infection is a significant public health problem around the world, especially in China. Previous research regarding the association of non-Hodgkin lymphoma (NHL) and HBV mostly focused on HBV antigen and HBV DNA. This study aimed to evaluate the relationship between HBV antibody and clinical prognosis in DLBCL. Methods: We retrospectively investigated the clinical characteristics of 190 newly diagnosed and untreated DLBCL patients and did a follow-up study. Results: Compared with HBeAb- patients, HBeAb+ patients displayed unique clinical features, such as more advanced disease stage (p=0.031) and higher International Prognostic Index (IPI) score (p=0.015). HBV antibody-negative patients had better therapeutic efficiency than positive patients (p<0.05). The media progression-free survival (PFS) and overall survival (OS) of HBV antibody-positive group were shorter than the negative group, respectively (p<0.05). Furthermore, we found positive association between CD21 and HBsAb (p=0.06) and their synergistic effect for prognostic predication. Interestingly, the effect of Rituximab in prognostic improvement was more significant in HBV antibody-positive group than negative group. Univariate analysis showed that HBV antibody status was independent risk factor for prognosis of DLBCL patients. Conclusions: Taken together, our investigations identified for the first time the close association between HBV antibody and clinical prognosis and Rituximab responses in DLBCL patients. These findings indicate the novel association between HBV infection and DLBCL prognosis, provide potential biomarker to predict the effect of Rituximab, and offer novel insights into the role of immune response to HBV infection in DLBCL progression.


Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4503-4506 ◽  
Author(s):  
Anja Mottok ◽  
Christoph Renné ◽  
Marc Seifert ◽  
Elsie Oppermann ◽  
Wolf Bechstein ◽  
...  

Abstract STATs are constitutively activated in several malignancies. In primary mediastinal large B-cell lymphoma and Hodgkin lymphoma (HL), inactivating mutations in SOCS1, an inhibitor of JAK/STAT signaling, contribute to deregulated STAT activity. Based on indications that the SOCS1 mutations are caused by the B cell–specific somatic hypermutation (SHM) process, we analyzed B-cell non-HL and normal B cells for mutations in SOCS1. One-fourth of diffuse large B-cell lymphoma and follicular lymphomas carried SOCS1 mutations, which were preferentially targeted to SHM hotspot motifs and frequently obviously inactivating. Rare mutations were observed in Burkitt lymphoma, plasmacytoma, and mantle cell lymphoma but not in tumors of a non–B-cell origin. Mutations in single-sorted germinal center B cells were infrequent relative to other genes mutated as byproducts of normal SHM, indicating that SOCS1 inactivation in primary mediastinal large B-cell lymphoma, HL, diffuse large B-cell lymphoma, and follicular lymphoma is frequently the result of aberrant SHM.


2018 ◽  
Vol 64 (6) ◽  
pp. 525-529 ◽  
Author(s):  
Natália Marcondes ◽  
Flavo Fernandes ◽  
Gustavo Faulhaber

SUMMARY OBJECTIVE: Ki-67 is a nuclear protein associated with cellular proliferation in normal or leukemic conditions that can help identify more aggressive diseases and is usually evaluated with immunohistochemistry. The aim of this was to assess Ki-67 expression on mature B-cell neoplasms samples with flow cytometry immunophenotyping. METHOD: After surface staining with CD19 and CD45, intracellular staining for Ki-67 was performed in leukemic mature B-cells. Ki-67 expression was evaluated with flow cytometry. RESULTS: Ki-67 expression was higher in mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma cases. It was also associated with CD38 mean fluorescence intensity. CONCLUSIONS: Ki-67 expression evaluated by flow cytometry can be a useful tool in the diagnosis of mature B-cell neoplasms. More studies are needed to validate Ki-67 assessment with flow cytometry immunophenotyping.


2019 ◽  
Vol 120 (12) ◽  
pp. 1137-1146 ◽  
Author(s):  
Anke Maes ◽  
Ken Maes ◽  
Hendrik De Raeve ◽  
Eva De Smedt ◽  
Philip Vlummens ◽  
...  

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 49-51 ◽  
Author(s):  
Tao Wang ◽  
Mingming Zhang ◽  
Jianrong Sun ◽  
Dong Hao ◽  
Zhijiang Qi ◽  
...  

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.


2012 ◽  
Vol 61 (4) ◽  
pp. 685-693 ◽  
Author(s):  
Shih-Chuan Hsiao ◽  
Inmaculada Ribera Cortada ◽  
Luis Colomo ◽  
Hongtao Ye ◽  
Hongxiang Liu ◽  
...  

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