Coexpression of MYC and BCL-2 predicts prognosis in primary gastrointestinal diffuse large B-cell lymphoma

• Published in: World journal of gastroenterology : WJG 2015-02, Vol.21 (8), p.2433-2442
• Main Authors: Xia, Bing, Zhang, Le, Guo, Shan-Qi, Li, Xiao-Wu, Qu, Fu-Lian, Zhao, Hai-Feng, Zhang, Lian-Yu, Sun, Bao-Cun, You, James, Zhang, Yi-Zhuo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Case-Control Studies; Chi-Square Distribution; China; Clinical Trials Study; diffus; Disease-Free Survival; Female; gastrointestinal; Gastrointestinal Neoplasms - chemistry; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - mortality; Gastrointestinal Neoplasms - pathology; Gastrointestinal Neoplasms - therapy; Hospitals, University; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Lymphoma, Large B-Cell, Diffuse - chemistry; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - pathology; Lymphoma, Large B-Cell, Diffuse - therapy; Male; Middle Aged; Multivariate Analysis; MYC; BCL-2; Survival; Primary; Neoplasm Staging; Predictive Value of Tests; Proportional Hazards Models; Proto-Oncogene Proteins c-bcl-2 - analysis; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-myc - analysis; Proto-Oncogene Proteins c-myc - genetics; Real-Time Polymerase Chain Reaction; Risk Factors; RNA, Messenger - analysis; Time Factors; Treatment Outcome; Young Adult
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v21.i8.2433

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.