Prognostic Significance Of MYC?BCL2 And P53 Expression In Diffused Large B-cell Lymphoma

Objective:This research was to investigate the interplay between the expression of MYC,BCL2 and P53 in diffuse large B-cell lymphoma(DLBCL),and study the impact of single or combined expression of these biomarkers on survival of patients with DLBCL.Methods:1.This study included 88 patients with de novo untreated DLBCL from 1st September,2012 to 31 th May,2018 in Shanxi Dayi hospital affiliated to Shanxi Medical University,including 46 men and 42 women with a median age of 63.5 years(range,14~96),47.7% patients had stage I~II disease,43.2% had stage III~IV disease.2.The diagnose of diffused large B-cell lymphoma was based on the 2018 World Health Organization(WHO)criteria.MYC?BCL2?P53?CD10?BCL6?MUM and Ki-67 expression were tested by IHC analysis.All patients received R-CHOP or CHOP-like immunochemotherapy.Response to therapy was evaluated after 4 cycles of treatment.Overall survival was calculated by measuring the time elapsed from the date of diagnosis until the date of death or last patient follow-up.3.Patient overall survival was analyzed by the Kaplan–Meier method and compared using the log-rank test.Chi-square test was used to determine the differences between variables.The prognostic effect of MYC,BCL2 and P53 expression was analyzed by univariate and multivariate analysis.Results:1.86 patients were designated as diffused large B-cell lymphoma,not otherwise specified,2 patients were designated as primary mediastinal large B-cell lymphoma.According to Hans classification,43.2% patients were GCB and 56.8% non-GCB.MYC,BCL2 and P53 expression was observed in 39 of 88(44%),44 of 88(50%)and 23 of 88(26%),respectively.21 of 88(24%)cases had MYC and BCL2 double expression,19 of 88(22%)cases had MYC and P53 co-expression,23 of 88(26.1%)cases had BCL2 and P53 co-expression,10 of 88(11.4%)cases had MYC,BCL2 and P53 triple expression.2.Compared with patients without P53 expression,those with P53 expression were associated with higher LDH and higher NCCN-IPI scores.3.Compared with patients without P53 expression,those with P53 expression had lower responses to chemotherapy,shorter overall survival and a higher rate of death(P<0.05).In patients who had diffuse large B-cell lymphoma associated with MYC,BCL2 expression or MYC+/BCL2+ double expression,P53 expression was associated with a significant worse overall survival compared with those without P53(P<0.05).Patients with lymphoma showing concurrent MYC and P53 expression had a worse prognosis compared with patients with either P53 or MYC expression alone(P<0.05).Patients with P53+/BCL2+ coexpression showed worse survival than patients with either P53 or BCL2 expression alone(P<0.05).In patients with MYC+/P53+ co-expression,BCL2 expression does not correlate with poorer survival significantly(P>0.05).Among patients with lymphoma with MYC+/P53+,MYC+/BCl2+ and BCL2+/P53+ co-expression,those with MYC+/P53+ coexpression had the worst overall survival(median OS: 21 months),followed by the subgroup of patients with MYC-/BCL2+/P53+(median OS: 35.5 months),patients with MYC+/BCL2+/P53-expression(median OS: 37.5 months)showed a longer OS compared with the other two subgroups(P<0.05).4.Multivariate analysis demonstrated that P53 expression and NCCN-IPI were independent prognostic factors in this patient cohort.Conclusion:1.P53 and MYC expression have a synergistically negative prognostic effect in diffused large B-cell lymphoma;2.BCL2 and P53 expression do not have such a synergistically effect;3.P53 expression is an independent prognostic factor in this cohort,patients with MYC+/P53+ expression showed a longer OS than those with MYC+/BCL2+ expression.P53 expression augments the negative prognostic effect of MYC+/BCL2+ double expression,patients with triple expression had a worse prognosis than those with double expression.