Correlation Between Expressions Of P-gp1 Protein,Gst-πprotein,p53 Protein,Ki-67 Protein And Clinicopathological Variables And Factors Of Multidrug Resistance In Diffuse Large B-cell Lymphoma

Background:Diffuse large B-cell lymphomas（DLBCL）are the most common lymphoid neoplasms in adults,accounting for approximately 32.5%of NHLs diagnosed annually.With highly invasive and advanced staging,the DLBCL have a poor prognosis.The first-line of treatment of DLBCL is immunochemical therapy with about 60%of cure rate^[1].However,since the existence of the multiple drug resistance（MDR）,almost 40%of patients have relapse or refractory.The mechanism of MDR of DLBCL is still not clearly defined.Various studies have been considered the association of protein expression with prognosis and overall survival in DLBCL,but not the clinical response after initial chemotherapy.To reverse the effect of MDR and increase the rate of complete response,it is necessary to make clear of the MDR mechanism.Objective:To determine the correlation between expressions of P-gp1 protein,Gst-πprotein,p53 protein,Ki-67 protein and clinicopathological variables and factors of multidrug resistance in Diffuse Large B-Cell Lymphoma.To conduct the clinical chemotherapy treatment by analysing the related factors of MDR.Materials and methods:We analyzed the expressions of P-gp1 protein,Gst-πprotein,p53 protein,Ki-67protein using immunohistochemistry in 48 pre-treatment tumor specimens obtained from de novo DLBCL patients treated at Dalian Medical University Affiliated 2nd hospital.According to the clinical data of the patients,and the 2008 World Health Organization classification,all patients are histopathological diagnosed DLBCL.Patients with only local extranodal lesions,primary central nervous system lymphoma,post-operation,no observable lesions,less than 4 cycles of chemotherapy,lost follow-up,and tissue specimens that could not meet the need of immunohistochemistry were excluded.There were only 48 eligible cases.48 patients were divided into two groups according to the curative effect of chemotherapy.The group consisted of complete remission（CR）and complete remission（CRu）group,and the other group was partial remission（PR）and stable（SD）and progressive disease（PD）groups.All tissue specimens were specimens before chemotherapy.We used streptavidin-biotin immunostaining as immunohistochemical method,analysing the expressions of P-gp1protein,Gst-πprotein,p53 protein,Ki-67 protein.Data analysis was performed by using the statistical package SPSS version 23.0 with Chi-square test,Fisher exact test.Results:1.Relationship between expressions of P-gp1 protein、Gst-πprotein、p53 protein,Ki-67 protein and clinicopathological variables.1.1 P-gp1 protein have no statistically significance with sex（p=0.101）,age（p=0.650）,extranodal lesions（p=0.945）,B symptom（p=1.000）,stage（p=0.285）,IPI（p=0.465）,LDH（p=0.629）,β2 microglobulin（p=0.268）and ESR（p=1.000）.1.2 Gst-πprotein have no statistically significance with sex（p=0.101）,age（p=0.313）,extranodal lesions（p=0.135）,B symptom（p=0.152）,stage（p=0.329）,IPI（p=0.291）,LDH（p=0.447）,β2 microglobulin（p=0.135）and ESR（p=0.096）.1.3 p53 protein have no statistically significance with sex（p=0.743）,age（p=0.743）,extranodal lesions（p=0.884）,B symptom（p=0.192）,stage（p=0.828）,IPI（p=0.343）,LDH（p=0.311）,β2 microglobulin（p=0.637）and ESR（p=0.730）.1.4 Ki-67 protein have no statistically significance with the clinicopathologic variables（p>0.05）,except ESR（p=0.004）.Other studied proteins have no statistically significance with the clinicopathologic variables（p>0.05）.2.Within clinicopathologic variables,stage is associated with clinical response（p=0.020）,other variables were not statistically significant（p>0.05）.3.The P-gp1 protein and Ki-67 protein were associated statistically with inferior clinical response after initial chemotherapy（p=0.034,p=0.014）.The association between Gst-πor p53 protein overexpression and clincal reponse were not statistically significant.（p=0.295,p=0.100）.The coexpression of Ki-67 and P-gp1 protein and coexpression of P-gp1 and p53 protein were associated statistically with inferior clinical response（p=0.000,p=0.015）.Other studied proteins combinations have no statistically significance with the clinical response（p>0.05）4.Based on origin,the cases divide into GCB（Germinal Center B-cell–like）and Non-GCB（Non-Germinal Center B-cell–like）groups（12 vs 36）.No statistically significance have been found between the origin and the expression of P-gp1 protein,Gst-πprotein,p53 protein and Ki-67 protein.Conclusions:1.High ESR group had a high expression of Ki-67 protein,and ESR may exhibit as an independent risk factor for expression of Ki-67 protein.2.The P-gp1 protein and Ki-67 protein overexpression group and their coexpression group had poor short-term responses and may exhibit as independent risk factors for multidrug resistance.P-gp1 protein and p53 protein coexpression had a poor short-term response and may exhibited as independent risk factors for multidrug resistance.3.Advanced stage group had a poor short-term response and may exhibited as independent risk factors for multidrug resistance.Patients with high ESR had worse response and ESR had a strong tendency towards statistical significance with short-term response.