| Background and Objective: Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma in the adult, the main clinical symptoms of DLBCL is progressive and painless lymphadenopathy. DLBCL is more common occur in old people, which the average age is 70 years old, and sometimes is also found in children. DLBCL is a type of highly aggressive tumors, About 70% of DLBCL can be cured through R-CHOP which is the line chemotherapy in clinical. But there are still nearly one-third of patients relapse in a short time, even worse, during treatment, the tumor is going to progress and relapse. Therefore, more and more researchers focus on the molecular biology and genetics of tumor cells to study the reason of tumorigenesis and drug resistance,and find a better redictors to analyzing prognosis of tumor and provide a new therapeutic targets and idea. Recent studies have found that MYD88 L265 P mutation is frequently occurring in a variety of B cell tumors, which is a gain of function mutation that result in such as NF-?B, JAK-STAT3 and so on signaling pathways are abnormally activated in the downstream, and associated with tumorigenesis, metastasis, drug resistance and prognosis of tumor. In the study, we detected the MYD88 L265 P mutation in DLBCL, to analysis the relationship between the mutation and the clinical and pathological features of DLBCL, and preliminarily probe correlation with treatment response of R-CHOP and prognosis with MYD88 L265 P mutation in DLBCL. Methods: 53 cases of diffuse large B-cell lymphoma with clinical data and paraffin blocks were selected from Sichuan Provincial Tumor Hospital during January 2007 to January 2015 in the research. All patients were initial diagnosis of DLBCL with CD20+ and treatment with at least 3 cycles of R-CHOP chemotherapy. MYD88 L265 P mutation was detected by PCR from the DNA which was extracted from paraffin-embedded tissues and analyzed the relationship between mutation and clinicopathological characters, treatment response and prognosis of DLBCL. Statistical analysis is through SPSS20 statistical software, which Mann-Whitney U test is for measurement data and count data by chi-square test, Fisher exact test, Log-rank univariate analysis and Cox multivariate analysis. Results: We successfully detected 16 cases carrying MYD88 L265 P mutation in 53 DLBCL, the mutation rate was 30.19%.Among the 16 mutation cases, there is 5 GCB and 11 Non-GCB DLBCL,12 cases were extranodal involvement(1case is located at testicular and 2 cases is at thyroid),occurring in spleen and mediastina each had 1case another. Statistical analysis, age and extranodal involvement is relevant with MYD88 L265 P mutation(X2=5.014,4.520;P=0.025,0.033),MYD88 L265 P mutation is more frequently occurring in the elderly and extranodal involvement patients. There is no significant difference between mutant and wild group in sex, B symptoms, Clinical stage, Pathological type, IPI score, ECOG score,LDH and Ki-67 levels, treatment response, recurrence and progression(P>0.05). To compare the treatment response of DLBCL standard first-line R-CHOP chemotherapy,the results showed that gender is associated with it(X2=4.802,P=0.035). Female have a better effect with R-CHOP than that of male. There is no significant difference of response to treatment in MYD88 L265 P mutant and wild group(P> 0.05). It suggests that there is no relationship between MYD88 L265 P mutation and tumor recurrence by further analysis the patients who have achieved CR/PR through first-line induction chemotherapy(P> 0.05).Log-rank univariate analysis show that there is a significant associations with PFS in B symptoms and Ki-67 subgroup(P = 0.004,0.030),but only B symptoms correlated with PFS after analyzed by the Cox multivariate analysis(P = 0.012).About MYD88 L265 P,there is no correlation with PFS and OS whether univariate or multivariate analysis(P>0.05) DLBCL. The median OS and PFS were 58.37 and 31.71 months in all patients of this study, and were 72 and 41.33 months in the wild group vs 40.16 and 27.84 months in MYD88 L265 P group. But, there is also no significant difference in wild and mutation group of the median survival time through Mann-Whitney U test(P=0.367,0.594). Conclusion:(1) MYD88 L265 P was frequently detected in DLBCL, especially in the subgroup of elderly and extranodal involvement have a higher frequency with MYD88 L265 P. MYD88 and the signaling pathway which depended may turn into a potential therapeutic target.(2)There is no significant correlation between MYD88 L265 P and response of first-line chemotherapy R-CHOP or disease progression and relapse.More research about molecular biology is needed to clarify the reasons of the subgroup that low treatment response with R-CHOP.(3)There is no correlation between MYD88 L265 P mutation and prognosis of DLBCL, the reasons of which had to been speculated were small number of cases, short follow-up time, selection bias or other relevant factors, so we will increase the sample size to verify the result next step. |
PDF Full Text Request