| BackgroundDiffuse large B-cell lymphoma(DLBCL)is the most common non-Hodgkin lymphoma,whose main prognostic factors are closely related to germinal center B-cell-like subtype(GCB-DLBCL)or activated B-cell-like type(ABC-DLBCL/non-GCB-DLBCL),as well as to “double-hit”(or “double expression”)or “triple-hit”(or “triple expression”).The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear.ObjectiveThis study aims to stratify primary central nervous system diffuse large B-cell lymphoma(PCNS-DLBCL)according to immunostaining algorithms of Hans,Choi and Meyer(Tally),and to investigate the multiple protein expression of C-MYC,BCL6,BCL-2,and the infection of EB virus and Borna virus,to explore the relationship between protein expression with COO subtype and prognosis as well as the relationship between PCNS-DLBCL and viral infection,further to elucidate the prognostic factors of primary central nervous system diffuse large B-cell lymphoma.MethodsNineteen cases of PCNS DLBCL in the Department of Neurosurgery of First Affiliated Hospital of Chongqing Medical University from April 2006 to July 2013,diagnosis according to the 2008 World Health Organization staging standards for hematopoietic and lymphoid tumors,were retrospectively studied.Immunochemical study was performed to measure the protein expression of BCL-6,CD10,MUM1,GCET1,FOXP1,LMO2,BCL-2,TP53,C-MYC as well as the protein co-expressions of C-MYC/BCL6/BCL2,BCL2/BCL6,C-MYC/BCL2 and C-MYC /BCL6 and follow-up information was analyzed.The EBV infection was detected by in situ hybridization,while detection of BDV infection by immunohistochemistry.The clinical informations and immunophenotypic features of all cases were summarized.According to immunostaining algorithms of Hans,Choi,and Meyer(Tally),nineteen cases of PCNS DLBCL were stratified.ResultsThe positive rates of C-MYC,BCL-6,BCL-2,MUM1 and FOXP1 in 19 patients with primary central nervous system diffuse large B-cell lymphoma were 78.9%,78.9% and 52.6%,84.2%,84.2%.Ki-67 index ranged from 10% to 70%,with mean value 45%.All of the cases were positive for CD20 and negative for CD3 and CD5,whereas only one(5.3%)case exhibited positive expression of TP53 and CD10.There were LMO2 expression and PD-L1 expression were only observed in 2 cases(10.5%)while PD-L2 was not expressed in any case.Furthermore,double expression of C-MYC/BCL-2 and C-MYC/BCL-6 were presented in 7(36.8%)and 11(57.9%)cases respectively,while triple expression of these three makers were observed in 6(31.6%)cases.Two cases infected with BDV but no one infected with EBV.By using different algorithms,all the cases were classified into GCB and ABC subtype.According to Hans algorithm,17(89.5%)cases were classified as ABC subtype versus 2(10.5%)cases as GCB;according to Choi algorithm,15(78.9%)cases were classified as ABC subtype versus 4(21.1%)cases as GCB;according to Tally Algorithm,16(84.2%)cases were classified as ABC subtype versus 3(15.8%)cases as GCB.And according to these algorithms,in ABC subtype,expression of C-MYC was presented in 12(12/17,70.6%),11(11/15,73.3%)and 11(11/16,68.8%)cases respectively;BCL-2 expression was observed in 10 cases(10/17,58.8%),10 cases(10/15,66.7%)and 10(10/16,62.5%)cases respectively;BCL-6 expression was observed in 13(13/17,76.5%)cases,13(13/15,86.7%)cases and 13(13/16,81.3%)cases respectively;double expression of C-MYC/BCL-2 was presented in 7(41.2%~46.7%)cases,both expression of C-MYC/BCL-6 and BCL-2/BCL-6 were presented in 9(52.9%~60%)cases respectively,while co-expression of these three makers were observed in 6(35.3% ~ 40%)cases.However,in GCB subtype,expression of C-MYC was presented in 2(2/2,100%)cases,3(3/4,75%)cases and 3(3/3,100%)cases respectively,BCL-6 expression was observed in 2(50%~100%)cases while BCL-2 was not expressed in any case.Double expression of C-MYC/BCL-6 was presented in 2(11.8%~13.3%)cases,no one with expression of C-MYC/BCL-2,BCL-2/BCL-6 and co-expression of C-MYC/BCL-2/BCL-6.The overall survival time of six patients with co-expression of C-MYC/BCL-2/BCL-6 ranged from 6 to 55 months(median,8.5 months),including one patient who had been alive and survived for 55 months and five patients who died after 6 to 32 months(median,8.5 months),whereas the overall survival time of thirteen patients without co-expression of C-MYC/BCL-2/BCL-6 ranged from 7 to 105 months(median,29 months),including ten patients who died after 7 to 52 months(median,28 months).Single factor survival analysis showed that there was no significant difference between C-MYC,BCL-2 and BCL-6 positive expression and prognosis.The corresponding P values were 0.972,0.555 and 0.625 respectively.The differences were not statistically significant.At the same time,survival analysis of C-MYC / BCL-2,C-MYC / BCL-6 and BCL-2 / BCL-6 showed that there was no significant difference between the double expression and the prognosis of patients.And the P values were 0.690,0.826,0.770 respectively,without statistical significance.Six patients with co-expression of C-MYC/BCL-2/BCL-6 had a worse prognosis compared to those without co-expression of C-MYC/BCL-2/BCL-6,although the diff erence was not statistically significant(p=0.268).ConclusionMost PCNS DLBCLs show activated B-cell-like subtype characteristics and have co-expressions of C-MYC/BCL6/BCL2,the subtype may be a major factor in its poor prognosis.In this study,PCNS DLBCL was not associated with EBV infection and Borna disease virus infection.In addition,PCNS DLBCLs with co-expression of C-MYC / BCL-2 / BCL-6 showed a worse overall prognosis than those without C-MYC / BCL-2 / BCL-6 co-expression.Therefore,the co-expression of C-MYC / BCL-2 / BCL-6 might be one of the most important features of PCNS DLBCL,which may help to further explore the relationship between immunological subtypes and the clinical prognosis of PCNS DLBCLs.At the same time,it can guide us to choose the more appropriate treatment to improve the curative effectand improve the prognosis effectively. |
PDF Full Text Request