Coexpression of MYC/Bcl-2 in Diffuse Large B-Cell Lymphoma: A Clinic Research

Backgroud

Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurred non-Hodgkin's lymphoma (NHL). With the development of chemotherapy and immunotherapy, some patients get a good prognosis, but still a considerable number of patients suffer from a strongly aggressive DLBCL with poor treatment effects. Due to the discovery of "double hit" of MYC/Bcl-2 genes, the coexpression of these two proteins has attracted more attention. Further investigations will be necessary to investigate the role of MYC/Bcl-2 co-expression in the clinical features of DLBCL as well as its relationship with prognosisto explore the significance of MYC/Bcl-2 protein coexpression in DLBCL.

Methods

89 confirmed DLBCL cases treated with the chemotherapy regimen of CHOP or R-CHOP between February 2008 and March 2014 were collected. Complete clinical data and paraffin-embedded tissues samples were available from these cases. immunohistochemistry analysis of MYC and Bcl-2 protein expression were carried out. In addition, the relationship between MYC/Bcl-2 protein coexpression and factors such as the age, gender, primary site, Ann Arbor staging, international prognostic index (IPI), immunohistochemical Hans type, and Ki-67 expression rate of patients were statistically analyzed in this paper. Furthermore, we investigated how the abovementioned indicators and whether or not Rituximab or MYC/Bcl-2 coexpression was applied were associated with the progression-free survival (PFS) and overall survival (OS) of patients.

Results

1. 89 cases with DLBCL were collected. The median age was 65 years with a range of 18-82. 54 cases were over 60 years old. 64 patients had a primary tumor in the lymph nodes .As per the IPI score, there were 30 low-risk cases (IPI<3). There were 27 cases at Ann Arbor stage I-II, 62 cases at stage III-IV, 31 GCB cases, 58 nonGCB cases. For 61 cases, the expression rate of Ki-67 was more than 70%.There were 41 cases treated with the chemotherapy regimen of R-CHOP and 48 cases treated with chemotherapy regimen of CHOP.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, 51cases (57.3%) had high Bcl-2 protein expression. There were 29 cases (32.6%) of MYC/Bcl-2 co-expression Compared with non-coexpression group, the median PFS (16m VS 33m, P<0.001) of the co-expression group decreased significantly.but there was not a significantly difference of the median OS. Moreover, Compared the MYC or Bcl-2 single expression group with the non-expression group, there were no significant differences among them.

3. Single factor analysis with other common risk factors indicated that in the high-risk group, including advanced aged (grouping by 60 years old)、treating without rituximab III-IV stages, and high IPI score, both PFS and OS decreased, and the difference was statistically significant (P<0.05); When 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. 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 risk factors to OS (P<0.05). However,MYC/Bcl-2 coexpression temporarily could not be considered as an independent risk factor for OS.

Conclusions

Bcl-2/MYC protein coexpression is significantly associated with IPI score of high-risk patients. Patients with MYC/Bcl-2 coexpression had a poorer prognosis than non-coexpression, with shortened PFS. They had a prognosis poorer than single high expressions of MYC or Bcl-2. The influence of MYC/Bcl-2 coexpression to the OS of DLBCL needs a longer follow-up time to study.MYC/Bcl-2 coexpression, IPI score, age, and use of rituximab, staging were independent prognostic factors to prognosis.