The Analysis Of Prognosis And Clinical Features In 81 Patients With Diffuse Large B-cell Lymphoma

Objective:The purpose of this study was to investigate MYC gene aberration,MYC protein expression, double-hit lymphoma(DHL) and double-protein expression lymphoma(DEL)in diffuse large B cell lymphoma(DLBCL),and their significance in the prognosis and clinical features.Methods:We detected MYC, BCL-2 genes by using interphase fluorescence in situ hybridization(FISH), and the protein markers including:CD10,MUM-1, Ki-67, BCL-6, BCL-2 and MYC by using immunohistochemistry(IHC) in the tissue of 81 patients with DLBCL,then analyzed by using statistical methods.Results:1.MYC gene aberration expression: in 81 patients with DLBCL,7cases were found MYC gene rearrangement(8.6%), 16 cases were found MYC gene amplification(19.8%),2 cases were found double-hit lymphoma(DHL)(2.47%). One had overall survival of 6.3 months,another one had overall survival of 8.0 months, DHL had a very poor prognosis compared to the cases without DHL.The cases with MYC gene rearrangement showed significantly shorter progression free survival(PFS) and overall survival(OS) compared to the cases without MYC gene rearrangement(PFS : P=0.013<0.05;OS : P=0.005<0.05). No significant difference was showed in PFS and OS between the case with MYC gene amplification and cases without MYC gene amplification(PFS:P=0.654>0.05;OS:P=0.648>0.05). Significant correlation wasfound between MYC gene rearrangement and clinical stage, the ratio of Stage Ⅲand Ⅳwith MYC gene rearrangement is higher than these without with MYC gene rearrangement. But no significant correlation was between MYC gene amplification and the clinical features.2. MYC protein expression: For the positive MYC protein expression of tumor cell, ≥30% was 36 cases(44.4%), ≥40% was 26cases(32.1%), ≥50% was 15 cases(18.5%). When the cut-off of MYC protein expression sets 30%,no significant difference was showed in PFS and OS between high protein expression and low protein expression(PFS:P =0.062>0.05;OS: P =0.109>0.05). When setting 40%, high protein expression showed significantly shorter PFS and OS compared to low protein expression(PFS: P =0.013<0.05;OS: P =0.017<0.05). When setting 50%, high protein expression showed significantly shorter PFS and OS compared to low protein expression(PFS: P=0.016<0.05; OS:P=0.011< 0.05). The cut-off of high expression was optimal for 40%.DEL was 19 cases(23.5%), which showed significantly shorter PFS and OS compared to the cases without DEL(PFS:P=0.004<0.05;OS:P=0.001 < 0.05).No Significant correlation was between MYC protein expression or DEL and the clinical features.3.High IPI was a poor predictor of PFS and OS in DLBCL. Both MYC gene rearrangement, MYC protein expression and DEL predicted poor PFS and OS, independently of the IPI(P <0.05).4. 7 patients with MYC gene rearrangement had 6 cases(85.7%)with high MYC protein expression, and above 60%; however,16 patients with MYC gene amplification only had 3 cases(18.75%) with high MYC protein expression. So MYC gene rearrangement was high correlation with MYC protein expression, MYC gene amplification was nocorrelation with MYC protein expression.Conclusion:1.In 81 patients with DLBCL, MYC gene rearrangement was 7/81(8.6%), MYC gene amplification was 16/81(19.8%), DHL was 2/81(2.47%), MYC protein expression(cut-off sets 40%) was 26/81(32.1%),DEL was 19/81(23.5%).2. MYC gene rearrangement predicted poor PFS and OS,independently of the IPI, but MYC gene amplification showed no impact on PFS and OS.3.MYC protein expression and DEL predicted poor PFS and OS,independently of the IPI, The cut-off of high expression was optimal for40%.4. MYC gene rearrangement showed significant correlation with clinical stage, the ratio of Stage Ⅲand Ⅳ with MYC gene rearrangement is higher than these without with MYC gene rearrangement.5.MYC gene rearrangement showed great correlation with MYC protein expression, there was great influenced between each other, MYC gene rearrangement may be a major factor to high MYC protein expression.