Expression And Clinical Significance Of CMYC,BCL2,BCL6 Protein In Diffuse Large B Cell Lymphoma

Objective Diffuse large B cell lymphoma is highly invasive and heterogeneity,and DLBCL has a great progress on treatment with the use of rituximab, but there are about one third of the patients with progression or death,This suggests that the existence of tumor cancer genes.There is close relationship between different immunological markers and the prognosis of DLBCL.So the aim of this study is to analysis CMYC, BCL2, the BCL6 protein expression for patients with DLBCL, and to investigate the relationship with the clinical features, immunophenotypic subtype and protein expression and analysis the clinical prognostic value.Methods The cases of 72 DLBCL pathological tissue samples with complete follow-up data newly from the First Affiliated Hospital of Anhui Medical University between January 2008 and December 2013 were retrospectively analyzed and the international prognostic index was analyzed.The patients were divided into GCB and non-GCB subtypes with the immunohistochemical method according to Hans. We assess the relationship between CMYC, BCL2, BCL6 protein expression levels and clinical characteristics, immunology and the the international prognostic index, and analyze the relationship between CMYC,BCL2 and BCL6 coexpression.In combination with Kaplan Meier method, the log rank test and multiariable Cox regression model of immunological indexes for survival analysis and treatment results and prognosis of single factor and multiple factors analysis.Results 1.The rate of CMYC、BCL2 and BCL6 protein positive expression was 29.2%, 58.3% and 68.1%,and the rate of CMYC/BCL2、CMYC/BCL6、CMYC/BCL2/BCL6 coexpression was 23.6%、18.1%、13.9% respectively. 2.The 3-year of OS and PFS were significantly lower in CMYC positive group than that in negative group(45.1% vs80.2%,P=0.002 and 30.5% vs 68.6%,P=0.008).Althoughthe 3-year OS had no significant difference between BCL2 positive group and negative group(61.3% vs 80.8%, P=0.055),the 3-year OS was significantly lower in BCL2 positive group than that in negative group(42.8% vs 76.7%, P=0.009).The 3-year of OS and PFS were significantly higher in BCL6 positive group than that in negative group(75.1% vs 57.8%,P=0.036 and 65.4% vs 39.0%,P=0.046), The 3-year of OS and PFS were significantly lower in CMYC/BCL2 coexpression group than that in non coexpression group(37.5% vs 79.9%,P=0.001 and 19.1% vs 69.1%,P=0.000), the 3-year OS and PFS had no significant difference between CMYC/BCL6 coexpression group and non coexpression group,CMYC/BCL2/BCL6 coexpression group and non coexpression group.3.Univariate analysis showed that CMYC positive, BCL6 negative, IPI high risk group, the non-GCB subtype and CMYC/BCL2 coexpression were associated with poor prognosis of the OS and PFS(P<0.05), and BCL2 positive was associated with poor prognosis of the PFS(P<0.05).Multivariate analysis showed that CMYC was an independent prognostic factor for OS and BCL2 was an independent prognostic factor for PFS, moreover, international prognostic index and CMYC/BCL2 coexpression were independent prognostic factors for OS and PFS.4. Survival analysis showed that the 3-year of OS and PFS were significantly worse in CMYC positive group than that in negative group for non-GCB subtype,difference was statistically significant(P = 0.001 and P = 0.009), and other various subgroups of CMYC positive group and negative group 3 years OS, PFS were no significant difference.Conclusion 1. The patients with DLBCL were divided into two kinds of immun-ophenotypic subtype with immunohistochemical method,and it could preliminaryly judge prognosis,and had a certain guiding significance to clinical therapy.2.Immunological indexes had certain prognostic value for patients with DLBCL.CMYC positive was one of independent poor prognostic factor for OS, BCL2 positive was one of independent poor prognostic factor for PFS.In addition,CMYC/BCL2 coexpression and IPI had influence up on OS and PFS.3.Immunophenotypic subtype combination CMYC had a certain guiding significance on prognosis,There was poor prognostic for patients with CMYC positive in non-GCB subtype group.4.CMYC, BCL2, BCL6 expression and CMYC/BCL2 coexpression are closely related to the development and prognosis of DLBCL, can be used as predict prognosis factors of DLBCL.