Clinicopathological Study Of CD30-positive Diffuse Large B-cell Lymphoma

Part ⅠPrevalence and Clinicopathologic features of CD30-positive de novo diffuse large B-cell lymphomaObjectives Diffuse large B-cell lymphoma(DLBCL),the most common type of non-Hodgkin lymphoma,is the most heterogeneous group of lymphomas with variable clinical conditions,pathological features and different response to immunochemotherapy.More efforts were required to build up useful molecular and/or immunophenotypic subgroups that could indicate prognosis and give clues about the therapy.Recently,CD30 expressing was reported in a group of DLBCLs predicting a new promising subtype.However,CD30 expression patterns and its prognostic significance were varied in the literature.We conducted the study to assess the prevalence of CD30 expression in de novo DLBCLs in East China and investigate the clinical and pathological features of CD3 0-positive DLBCL.Methods This study retrospectively analyzed consecutive cases of de novo DLBCL diagnosed between October 2006 and December 2015,from the Departments of Pathology of The First Affiliated Hospital of Nanjing Medical University.All cases were diagnosed according to the World Health Organization(WHO)criteria and reviewed by two senior hematopathologists.Using the method of immunohistochemistry,we assessed the expression of CD30 in formalin-fixed paraffin-embedded tissues.Morphological features of DLBCLs and the pattern of CD30 expression were observed microscopically.Chi-squared and Fisher exact test were used to see the correlation between CD30 expression and clinical pathological features.Results Applying a>0%threshold,CD30 was expressed in 11.54%patients of de novo DLBCL.If using a>=20%threshold,CD30 was expressed in 9.5%DLBCL patients.CD30 positive DLBCLs tended to affecting younger people(<60yrs),with fewer number of B symptoms and elevated serum LDH.Morphologically,CD30 positive DLBCL mainly presented as centroblastic or anaplastic variant.Conclusions CD30 can express in de novo DLBCL and CD30 positive DLBCL has characteristic clinical pathological features.Part ⅡImmunophenotype of CD30 positive DLBCL and its correlation with MYC,BCL2 gene alterationsObjectives To investigate the immunophenotypical features of CD30-positive DLBCL and find the correlation between CD30 expression and the cell of origin(COO),MYC and BCL2 protein expression,and their gene alterations as well.Methods Using the method of imunohistochemistry,we assessed the expression of a panel of immunohistochemical markers,such as CD5,CD 10,BCL6,MUM1/IRF4,FOXP1,GCET1,LM02,BCL2,MYC,Ki67,in formalin-fixed paraffin-embedded tissues.Additionally,MYC and BCL2 gene translocation and amplification were analyzed by using fluorescence in situ hybridization(FISH).Chi-squared and Fisher exact test were used to see correlation between CD30 expression and immunophenotypical and genetic features.Results CD30 expression in DLBCL did not correlate with cell of origin,but CD30 positive DLBCL showed a lower frequency of BCL2 and MYC expression.Furthermore,lower frequency of BCL2 expression was predominately observed in non-GCB subtype and correlated with lower frequency of BCL2 gene amplification.Lower frequency of MYC expression was mainly in GCB subtype and correlated with the absence of MYC gene translocation.Conclusions CD30 positive DLBCL has characteristic immunophenotypical and genetic features,with lower frequency of BCL2 gene amplification,absence of MYC gene translocation,and correspondingly lower frequency of BCL2 and MYC protein expression.Part ⅢPrognostic analysis of DLBCLs with CD30 positive expressionObjectives To analyze the prognostic value of CD30 in DLBCLs and find its correlated influences.Methods 232 cases of de novo DLBCLs were analyzed retrospectively and the prognostic value of CD30 and related factors were investigated using the Kaplan-Meier method and Cox regression analysis.Results Generally,patients with CD30 expression showed significantly superior OS and PFS comparing to those with CD30-negative,although the prognostic value of CD30 was affected by IPI score,BCL2 protein expression and MYC gene alterations.Stratified analyses showed that statistical significance between CD30 positive DLBCL and CD30 negative DLBCL were only observed in BCL2 protein negative group and the no MYC gene alterations group.Conclusions CD30 may be a superior prognostic marker of de novo DLBCL and its function maybe correlate with lower expression of BCL2 protein and absence of MYC gene translocation.Further studies should be performed to evaluate the feasibility of anti-CD30 targeted treatment in DLBCL therapy,especially in BCL2 positive and MYC alteration DLBCLs.