Prognostic Correlation Research Of MYC/Bcl-2 Coexpression In DLBCL

【Objective】Diffuse large B-cell lymphoma(DLBCL) is the most commonly seen non-Hodgkin’s malignant lymphoma(NHL). On the basis of chemotherapy and immunotherapy,some patients have a good prognosis, but still a considerable number of patients suffer a strongly aggressive DLBCL with poor treatment effects. Since the overall prognosis presents considerable heterogeneity, more ideal prognostic indicators should be found for better risk stratification. Recently, MYC / Bcl-2 protein coexpression has attracted more attention on the basis of the “double whammy” of MYC, Bcl-2 genes. In this paper, MYC/Bcl-2 coexpression and the clinical features of DLBCL and its relationship with prognosis are studied, in the hope of exploring the significance of MYC/Bcl-2 protein coexpression in DLBCL.【Methods】89 confirmed DLBCL cases were collected, which were equipped with complete clinical data and available paraffin-embedded tissues samples and admitted in the Hematology Department of Hangzhou First People’s Hospital between February 2008 and March 2014. Immunohistochemical examinations of MYC and Bcl-2 protein expression were carried out. In addition, this paper made a statistical analysis of the relationship between MYC/Bcl-2 protein coexpression and such factors as the age,gender, primary site, Ann Arbor staging, international prognostic index(IPI),immunohistochemical Hans type, and Ki-67 expression rate of patients. Further, it investigated how the abovementioned indicators and whether or not Rituximab or MYC/Bcl-2 coexpression was applied was associated with the progression-free survival(PFS) and overall survival(OS) of patients. According to the data, Kaplan-Meier survival curve was drawn and compared with log-Rank for the survival rate. For multivariate analysis, the COX regression model was employed to determine the independent prognostic factors.【Result】1.89 cases of patients with DLBCL were collected. The median age was 65 years with a range of 18-82. There were 59 males and 49 females; 54 cases were over 60 years old, and 35 cases were less than 60 years old; 64 patients had a primary tumor in the lymph nodes and 25 patients had a primary tumor outside the lymph nodes. As per the IPI score, there were 59 high-risk cases and 30 low-risk cases. There were 27 cases at Ann Arbor stage I-II, 62 cases at stage III-IV, 31 GCB cases, 58 non GCB cases, 64 cases of primary lymph nodes, 25 cases of outside lymph nodes. For 61 cases, the expression rate of Ki-67 was more than 70% and for 28 cases, the expression rate of Ki-67 was less than 70%. MYC/Bcl-2 coexpression was associated with high-risk IPI score(P = 0.022).2. 37 cases had high MYC protein expression, accounting for 41.5%. Also, 51 cases had high Bcl-2 protein expression, accounting for 57.3%. There were 29 cases of MYC/Bcl-2 co-expression, accounting for 32.6%. Comparing MYC/Bcl-2coexpression group with non-coexpression group, the median PFS(11.5m VS 29 m,P=0.002) and OS(25m VS N/A, P=0.01) decreased significantly. Moreover,comparing MYC/Bcl-2 coexpression group with the MYC protein expression and Bcl-2 single expression group, it was found that in the coexpression group median PFS was less than the MYC group and Bcl-2 single expression group(P <0.05), while the median OS declined, showing no statistically significant differences(P> 0.05).3. It was found from a single factor analysis of other common risk factors that advanced aged(grouping by 60 years old), III-IV stages, and IPI score, both PFS and OS decreased in the high-risk group, and the difference was statistically significant(P<0.05); grouping by immunohistochemical Hans classification, primary site and Ki-67 expression(divided by 70%), OS comparison of the two groups showed no significant difference(P> 0.05).4. Statistically different factors were included in the multivariate regression analysis.It was found that MYC/Bcl-2 coexpression, IPI score, age, and use of rituximab,staging were independent prognostic factors to PFS(P <0.05), while IPI score, staging and age were independent prognostic factors to OS(P<0.05). What’s more, MYC/Bcl-2 coexpression temporarily could not be considered as an independent risk factor for OS.【Conclusions】1.Bcl-2/MYC protein coexpression is significantly associated with IPI score of high-risk patients, but not with gender, advanced age, Han typing, Ann Arbor staging,whether within primary lymph nodes, and Ki-67 expression rate, etc.2.MYC/Bcl-2 coexpression has a poorer prognosis than non-coexpression, shortens PFS and OS, and has poorer single high expressions of MYC and Bcl-2;3.Rituximab, age, Ki-67 expression, primary site, staging, and MYC/Bcl-2coexpression are all likely to cause poor prognosis of DLBCL; MYC/Bcl-2coexpression, IPI score, staging and age are independent prognostic risk factors that shorten PFS; IPI score, stage, age are independent prognostic risk factors that shorten OS.