| Objective:Diffuse Large B Cell Lymphoma(DLBCL) has the significant biological heterogeneity of treatment sensitivity and prognosis which closely associate with various immunophenotypes and expression level of ki-67、bcl-2. The introduction of the monoclonal CD20 antibody rituximab in chemotherapies may significantly improve the survival of DLBCL, and therefore, the prognostic index based exclusively on traditional chemotherapies remains to be re-evaluated. The aim of this study is to investigate prognostic significance of immunohistochemical markers and immunophenotypes in patients with DLBCL and prognostic impact of rituximab on immunohistochemical markers.Method:One-hundred and eighty-six cases of de novo DLBCL with complete clinical data and follow-up records diagnosed from January 2005 to December 2013 at the People’s Hospital of Xinjiang Uyghur Autonomous Region were retrospectively analyzed and the international prognostic index(IPI) score was re-evaluated. All patients were divided into chemotherapy group(CHOP) and immune chemotherapy group(RCHOP) according to the therapeutic schedule. Antibodies to CD45 RO,CD3, CD5, CD20, CD79 a, Bcl-2, Ki-67, Bcl-6, CD10 and MUM1 were applied for immunophenotype analysis. Germinal center B-cell-like(GCB) and non-GCB subtypes were classified using an algorithm proposed by Hans. Expression level of bcl-6, CD10, MUM-1 and the prognostic value of immunophenotypes, bcl-2, ki-67 and IPI scorebetween the GCB and non-GCB subgroups were assessed by using the Kaplan-Meier method and Cox regression analysis.Result:1. A total of 186 DLBCL patients: 84 were treated with CHOP regimen and rituximab was added to the CHOP regimen(R-CHOP regimen) in 102 cases. The 5-year OS rates of patients treated with R-CHOP regimen were significantly higher than of those treated with the CHOP regimen(65.69 vs. 42.86 %, P<0.01). 2. The 5-year OS rate of the GCB subtype patients in the CHOP group was significantly higher than that of the non-GCB subtype(58.82 vs. 32.00 %,P = 0.004) while there was no significant differences of 5-year OS rates were observed between GCB and non-GCB subtype patients in the R-CHOP group(72.97 vs. 61.54 %,P=0.101). Further analysis showed that non-GCB subtype patients treated with R-CHOP had significantly higher 5-year OS rates than those treated with CHOP regimen(c2=7.385,P=0.007), while there was no significant difference in 5-year OS rates of GCB subtype patients between the R-CHOP and CHOP groups(c2=1.304,P=0.253).3. In the 107 low risk group, 47 were treated with CHOP regimen and 70 were treated with RCHOP regimen.There was no significant difference in 5-year OS rates between GCB and non-GCB subtype patients in the CHOP group(c2=1.531,P=0.216),and likewise, there was no significant difference in 5-year OS rates between the two subtypes in the RCHOP group(c2=0.762,P=0.383); Further analysis showed that there was no significant difference in 5-year OS rates between the CHOP and R-CHOP groups in the GCB and non-GCB subtypes(c2=0.867,P=0.352;c2=2.828,P=0.093).In the 79 hige risk group, 37 and 42 cases of the patients were classified in CHOP and RCHOP group respectively, the 5-year OS rate of the GCB subtypes was significantly higher than that of the non-GCB subtype in the CHOP group(c2=3.978,P=0.045),while there was no significant difference in 5-year OS rates between GCB and non-GCB subtype patients in the RCHOP group(c2=0.762,P=0.383); Further analysis showed that there was nosignificant difference in 5-year OS rates between the CHOP and R-CHOP groups in the GCB and non-GCB subtypes(c2=1.336,P=0.248;c2=1.873,P=0.171)4.Cox multivariable analysis showed that, ki-67 expression(HR=0.910,95%CI=1.334-4.623, P=0.004) and IPI scores(HR=0.669, 95%CI=1.059-3.599,P=0.032) in the CHOP group,ki-67 expression(HR=0.858,95%CI=1.078-4.521,P=0.030)and IPI scores(HR=1.203,95%CI= 1.609-6.889,P=0.001) in the RCHOP group,both were independent prognostic factors in these two treatment groups and had significant prognostic value for OS.5.Survival analysis showed that, in the CHOP treatment group, non-GCB subgroup Bcl-2-negative patients had significantly longer overall survival times than Bcl-2-positive patients(P= 0.025), while in the other subgroups there was no significant differences existed between Bcl-2 positive and Bcl-2 negative patients.Conclusion: 1. By using immunohistochemistry, de novo DLBCL can be divided into two immunophenotype subgroups which have guiding significance for early prognostication and therapeutic strategies, but, which no longer retain their prognostic significance and could be weakened during the postrituximab era. 2.Survival of non-GCB subgroup was significantly improved when treated with R-CHOP rather than CHOP alone. However, it needs to be further explored in the case of GCB subgroup. 3. Immunohistochemical markers were significant prognostic parameter in DLBCL, ki-67≥60% and IPI scores hige risk group were independent adverse prognostic factors in both CHOP and R-CHOP group while combination with immunophenotyping and Bcl-2 expressions can be used for predicting the clinical outcome in DLBCL patients. 4.Addition of rituximab can improve the therapeutic outcome particularly for non-GCB Bcl-2 positive subtype DLBCL patients due to Bcl-2 was overexpressed in non-GCB subgroup and rituximab appears to overcome and negates the adverse prognostic influence of Bcl-2 over expression in in non-GCB DLBCL. |
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