AIM:To investigate whether MYC and BCL-2 coexpression has prognostic significance in primary gastrointestinal diffuse large B-cell lymphoma(PGI-DLBCL)patients,and explore its associations with patients’clinical param...AIM:To investigate whether MYC and BCL-2 coexpression has prognostic significance in primary gastrointestinal diffuse large B-cell lymphoma(PGI-DLBCL)patients,and explore its associations with patients’clinical parameters.METHODS:Fresh and paraffin-embedded tumor tissue samples from 60 PGI-DLBCL patients who had undergone surgery at the Tianjin Medical University Cancer Institute and Hospital from January 2005 to May 2010 were obtained,and 30 lymphoid tissue samples from reactive lymph nodes of age-and sexmatched patients represented control samples.Staging and diagnostic procedures were conducted according to the Lugano staging system.All patients had been treated with three therapeutic modalities:surgery,chemotherapy,or radiotherapy.Expression of MYC and BCL-2 were detected at both protein and m RNA levels by immunohistochemistry and real-time RT-PCR.RESULTS:Positive expression levels of MYC and BCL-2proteins were detected in 35%and 45%of patients,respectively.MYC+/BCL-2+protein was present in30%of patients.MYC and BCL-2 protein levels were correlated with high MYC and BCL-2 m RNA expression,respectively(both P<0.05).We found that advancedstage disease(atⅡE-Ⅳ)was associated with MYC and BCL-2 coexpression levels(P<0.05).In addition,MYC+/BCL-2+patients had more difficulty in achieving complete remission than others(P<0.05).Presenceof MYC protein expression only affected overall survivaland progression-free survival(PFS)when BCL-2 proteinwas coexpressed.The adverse prognostic impact ofMYC+/BCL-2+protein on PFS remained significant(P<0.05)even after adjusting for age,Lugano stage,international prognostic index,and BCL-2 proteinexpression in a multivariable model.CONCLUSION:MYC+/BCL-2+patients have worsechemotherapy response and poorer prognosis thanpatients who only express one of the two proteins,suggesting that assessment of MYC and BCL-2 expressionby immunohistochemistry has clinical significance inpredicting clinical outcomes of PGI-DLBCL patients.展开更多
Myc and p53 proteins are closely associated with many physiological cellular functions,including immune response and lymphocyte survival,and are expressed in the lymphoid organs,which are sites for the development and...Myc and p53 proteins are closely associated with many physiological cellular functions,including immune response and lymphocyte survival,and are expressed in the lymphoid organs,which are sites for the development and activation of B-cell malignancies.Genetic alterations and other mechanisms resulting in constitutive activation,rearrangement,or mutation of MYC and TP53 contribute to the development of lymphomas,progression and therapy resistance by gene dysregulation,activation of downstream anti-apoptotic pathways,and unfavorable microenvironment interactions.The cross-talk between the Myc and p53 proteins contributes to the inferior prognosis in many types of B-cell lymphomas.In this review,we present the physiological roles of Myc and p53 proteins,and recent advances in understanding the pathological roles of Myc,p53,and their cross-talk in lymphoid neoplasms.In addition,we highlight clinical trials of novel agents that directly or indirectly inhibit Myc and/or p53 protein functions and their signaling pathways.Although,to date,these trials have failed to overcome drug resistance,the new results have highlighted the clinical efficiency of targeting diverse mechanisms of action with the goal of optimizing novel therapeutic opportunities to eradicate lymphoma cells.展开更多
基金Supported by National Natural Science Foundation of China,No.30672208,No.81270603 and No.31301161Tianjin Natural Science Foundation of China,No.13JCYBJC22800
文摘AIM:To investigate whether MYC and BCL-2 coexpression has prognostic significance in primary gastrointestinal diffuse large B-cell lymphoma(PGI-DLBCL)patients,and explore its associations with patients’clinical parameters.METHODS:Fresh and paraffin-embedded tumor tissue samples from 60 PGI-DLBCL patients who had undergone surgery at the Tianjin Medical University Cancer Institute and Hospital from January 2005 to May 2010 were obtained,and 30 lymphoid tissue samples from reactive lymph nodes of age-and sexmatched patients represented control samples.Staging and diagnostic procedures were conducted according to the Lugano staging system.All patients had been treated with three therapeutic modalities:surgery,chemotherapy,or radiotherapy.Expression of MYC and BCL-2 were detected at both protein and m RNA levels by immunohistochemistry and real-time RT-PCR.RESULTS:Positive expression levels of MYC and BCL-2proteins were detected in 35%and 45%of patients,respectively.MYC+/BCL-2+protein was present in30%of patients.MYC and BCL-2 protein levels were correlated with high MYC and BCL-2 m RNA expression,respectively(both P<0.05).We found that advancedstage disease(atⅡE-Ⅳ)was associated with MYC and BCL-2 coexpression levels(P<0.05).In addition,MYC+/BCL-2+patients had more difficulty in achieving complete remission than others(P<0.05).Presenceof MYC protein expression only affected overall survivaland progression-free survival(PFS)when BCL-2 proteinwas coexpressed.The adverse prognostic impact ofMYC+/BCL-2+protein on PFS remained significant(P<0.05)even after adjusting for age,Lugano stage,international prognostic index,and BCL-2 proteinexpression in a multivariable model.CONCLUSION:MYC+/BCL-2+patients have worsechemotherapy response and poorer prognosis thanpatients who only express one of the two proteins,suggesting that assessment of MYC and BCL-2 expressionby immunohistochemistry has clinical significance inpredicting clinical outcomes of PGI-DLBCL patients.
基金This work was supported by the National Natural Science Foundation of China 81460030 and 81770221 to LY.
文摘Myc and p53 proteins are closely associated with many physiological cellular functions,including immune response and lymphocyte survival,and are expressed in the lymphoid organs,which are sites for the development and activation of B-cell malignancies.Genetic alterations and other mechanisms resulting in constitutive activation,rearrangement,or mutation of MYC and TP53 contribute to the development of lymphomas,progression and therapy resistance by gene dysregulation,activation of downstream anti-apoptotic pathways,and unfavorable microenvironment interactions.The cross-talk between the Myc and p53 proteins contributes to the inferior prognosis in many types of B-cell lymphomas.In this review,we present the physiological roles of Myc and p53 proteins,and recent advances in understanding the pathological roles of Myc,p53,and their cross-talk in lymphoid neoplasms.In addition,we highlight clinical trials of novel agents that directly or indirectly inhibit Myc and/or p53 protein functions and their signaling pathways.Although,to date,these trials have failed to overcome drug resistance,the new results have highlighted the clinical efficiency of targeting diverse mechanisms of action with the goal of optimizing novel therapeutic opportunities to eradicate lymphoma cells.
