Clinical And Pathological Characteristics Of De Novo DLBCLs With Decreased CD20 Cell Surface Expression

Background and objective:Diffuse large B cell lymphoma(DLBCL) is the most common subtype of non-Hodgkin’s lymphoma(NHL), is a remarkably heterogeneous disease with considerable variation in clinical behavior, response to therapy, and long-term outcome. CD20 is a cell surface antigen expressed specially on most human B cells. CD20 is also expressed on 90%-95% de novo DLBCL cells, so CD20 has become a good molecular target for rituximanb which is a mouse-huaman chimeric monoclonal antibody targeting CD20. Previous researches indicate that the level of CD20 expression is correlated with the efficacy of rituximab. Both immunohistochemistry (IHC) and flow cytometry (FCM) are used in detecting CD20. Some diffuse large B cell lymphoma(DLBCL) patients show discordant CD20 protein expression showing an immunohistochemistry(IHC)-positive and flow cytometry(FCM)-negative or dim. In this study, we analysed the clinicopathological feature of diffuse large B cell lymphoma with cytomembrane surface CD20 protein decreased.Methods:Between 2011 and 2013, patients were diagnosed with DLBCL showing a CD20 immunohistochemistry positive and flow cytometry immunophenotyping negative in Fudan University Shanghai Cancer Center. All the patients were retrospectively analysed. The clinical data were reviewed including therapeutic regiment, efficacy of the treatment, Intenational Prognostic Index(IPI), individual biomarker(BCL-2, BCL-6, CD 10, MUM1). According to the result of CD20 FCM, patients were divided into CD20FCM(bright+) and CD20FCM(dim+/-) two groups. We made the comparison of IHC immunophenotype feature between the two groups. The clinical course were defined as follows:patients achieving complete response(CR) or partial response(PR); patients achieving stable disease(SD) or progress disease(PD). We defined CR+PR as positive response, SD+PD as negative response. We compared the difference of CD20 protein expression detecting by FCM between positive and negative response groups. We analyzed the data with SPSS 19.0 software. Chi-square test or Fisher’s exact test was used to compare categorical variables among groups. Influencing factors of curative effect were analysed using univariable and multivariable logistic regression analysis. Survival analysis was performed by Kaplan-Meier methods. Multivariate Cox proportional-hazards model was used to determine the independent prognostic factors.Results:Between 2011 and 2013,88 patients were diagnosed with the diffuse large B cell lymphoma with CD20 immunohistochemistry positive and flow cytometry immunophenotyping negative. Patients were divided into two groups:group A:34 patients with CD20FCM(-) phenotype,16 patients were treated in Fudan University Shanghai Cancer Center and were followed up; group B:54 patients with CD20 FCM(+) phenotype,27 patients were treated in Fudan University Shanghai Cancer Center and were followed up. The positive rate of BCL6 in group A and B is 73% and 96% respectively, there was significant difference (p=0.012). The positive rate of CD20 protein detecting by FCM in positive response group and negative response group is 66% and 50%, there was no significant difference (p=0.407). There was no curative effect influencing factors in logistic regression analysis. CD20FCM、age and IPI were prognostic factors in survival analysis.Conclusions:The positive rate of BCL6 in CD20-IHC(+)FCM(+) DLBCL is much higher than in CD20-IHC(+)FCM(-) DLBCL; the CD20 protein expression detecting by FCM was no difference between positive response and negative response group; CD20FCM、age and IPI were independent prognostic factors in DLBCL.