| Diffuse large B cell lymphoma(DLBCL)is the most frequent type of non-Hodgkin’s lymphoma,accounts for approximately 40 percent of new cases of non-Hodgkin’s lymphoma.Its pathogenesis is associated with a variety of pathogenic and biochemical factors with the characteristics of rapid development and high invasiveness.Epstein–Barr virus(EBV),first isolated by Epstein et al.in 1964,is a double-stranded DNA virus belonging to the human herpes virus family.EBV has been reported to be associated with several malignancies and accumulated evidence has shown the importance of Epstein–Barr virus in the pathogenesis of various lymphomas including DLBCL.This study aimed to retrospectively analyze the clinical information of patients with EBV+DLBCL and to find out the clinical features of EBV+DLBCL.We focused on the level of gene and protein expression,trying to discover the pathogenesis of EBV+DLBCL,and lay the foundation for further exploration of the effective treatment.This study is divided into two parts.In the first part,we collected pathological specimens of patients with newly diagnosed DLBCL and detected the expression of EBV in DLBCL.We analyzed the role of EBV on the prognosis of DLBCL.In the second part,we studied expression of P53 and the mutation of TP53 gene with the cases of EBV+DLBCL,so as to explore the possible pathogenesis.Part Ⅰ The expression of EBV and prognosis of DLBCL Objective: To figure out the rate of EBV+DLBCL and analyse the prognostic value of EBV in DLBCL.Methods: We performed a retrospective study included 346 patients who were newly diagnosed of DLBCL between January 2011 and December 2015.Epstein-Barr encoding region(EBER)in situ hybridization method was used to detect EBV expression in the pathological specimens of these patients.Combined with clinical and pathological information,we analyzed the the prognostic value of EBV in DLBCL.Results: Among the 346 patients,there were 36 EBV+ DLBCL patients(10.4%).The spearman correlation analysis of EBV and other clinical characteristics showed that EBV is not related with age,gender,Hans subtype,“double-expression” subtype,ECOG score,Ann Arbor stage,IPI score,LDH,and β2-MG.The Cox Regression showed that EBV is an independent prognostic factor in DLBCL patients.Conclusion: The rate of EBV+ DLBCL patients was 10.4%,and EBV was an independent prognostic factor of DLBCL patients.Part Ⅱ P53 deregulation and TP53 Gene Mutations analysis in EBV-Positive Diffuse Large B-Cell Lymphoma Objective: Detect the expression of P53 and analyze the mutations of TP53 gene in EBV+DLBCL so as to find the possible pathogenesis.Methods: A case-control study was performed with DLBCL patients.P53 expression was detected by immunohistochemistry(IHC),and TP53 mutations were investigated using the DNA Sanger sequencing method.Results: 1.P53 expression: P53 was positive in 24 of all 72 cases(33.3%).Respectively,there were 16 cases(44.4%)in EBV+ group,and 8 cases in EBV-group(22.2%).The positive rate of P53 in EBV+ group was significantly higher than that in EBV-group(44.4% vs22.2%,p = 0.046).2.TP53 gene mutations: Among EBV+DLBCL patients,the rate of TP53 gene mutations is 18.8%.Conclusion: The positive rate of P53 expression in EBV+ group was 44.4%.And the rate of TP53 mutation in EBV+ group is relatively low(18.8%).The high positivity of P53 in EBV+ DLBCL revealed that the abnormal activation of P53 pathway could be one of the possible pathogenesis of EBV+DLBCL.Meanwhile,the low rate of TP53 mutation confirmed that the mutation maybe not the cause of the abnormality of P53 pathway in EBV+DLBCL,which may be caused by some other factors.According to the significantly difference of P53 positivity between EBV+DLBCL and EBV-DLBCL groups,EBV infection is likely to be closely related to P53 expression.Abnormalities of P53 pathway induced by EBV may be a possible pathogenesis of EBV+DLBCL. |
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