The Relationship Between CD68 Expression And Microvessel Density And Beclin-1 In The Microenvironment Of Diffuse Large B-cell Lymphoma

Objective:To investigate the relationship between CD68 expression and microvessel density(MVD)and Beclin-1 in the microenvironment of diffuse large B-cell lymphoma(DLBCL).Methods:Immunohistochemical staining(IHC)was used to detect the expression of CD68,CD34 and Beclin-1 in 77 DLBCL patients.Chi-square test was performed to analyze the correlations between CD68,CD34 and Beclin-1 with clinicopathological factors(age,gender,primary site,immunophenotype,Ann Arbor stage,IPI,B symptoms and lactate dehydrogenase).Spearman correlation analysis was used to evaluate the relationship between CD68 and MVD.Paired Chi-square test was used to analyze the association between Beclin-1 and CD68 or MVD.Results:1.CD68 expression was associated with age(?2=5.826,P=0.016)and International Prognostic Index(IPD(?2=9.480,P=0.002);MVD was related to the primary site(?2=9.506,P=0.002)and IPN(?2=4.696,P=0.030);Beclin-1 was not associated with any clinicopathological parameters.The correlation analysis showed that CD68 was positively correlated with MVD(r=0.290,P=0.010),and Beclin-1 expression was not correlated with CD68 or MVD.2.In germinal center B-cell-like(GCB)DLBCL,CD68 expression was related to IPI(?2=6.363,P=0.012);MVD was related to the primary site(?2=4.659,P=0.031)and IPI(?2=6.060,P=0.014);Beclin-1 was not related to any clinicopathological parameters.The correlation analysis showed that CD68 was positively correlated with MVD(r=0.403,P=0.013),and Beclin-1 was not correlated with CD68 or MVD.3.In non-germinal center B-cell-like(non-GCB)DLBCL,CD68 expression was related to IPI(?2=5.105,P=0.024);Both MVD and Beclin-1 were not correlated with any clinicopathological parameters.The results of correlation analysis showed that CD68 was not related to MVD,and Beclin-1 expression was not associated with CD68 or MVD.Conclusion:1.The number of CD68-positive macrophages was related to age and IPI.MVD was related to the primary site and IPI.The infiltration of CD68-positive macrophages in DLBCL microenvironment is associated with tumor angiogenesis.The increased number of CD68-positive macrophages and MVD may indicate adverse prognosis of patients.2.In GCB DLBCL,the number of CD68-positive macrophages was related to IPI.MVD was related to the primary site and IPI.CD68-positive macrophages infiltration was correlated with tumor angiogenesis.Increased number of CD68-positive macrophages and high expression of MVD may indicate poor prognosis of patients.3.In non-GCB DLBCL,the number of CD68-positive macrophages was still related to IPI.High expression of CD68-positive macrophages indicated unfavorable outcome of patients.Background:Angiogenesis is essential for growth and progression of tumor.Angiogenesis in non-Hodgkin lymphoma(NHL)has been investigated by a variety of studies.However,the correlations between angiogenesis and the occurrence or prognosis of NHL remains controversial.Methods:A systematic and comprehensive retrieval of relevant literatures from PubMed,EMBASE and Web of science databases was performed.The quality of the eligible studies was assessed using Newcastle-Ottawa Scale(NOS).The difference of microvessel density(MVD)in NHL group and control group(lymphadenitis and normal lymph nodes)was assessed by standardized mean difference(SMD).The odds ratio(OR)was used to evaluate the relationship between MVD and disease stage.The hazard ratio(HR)was used to assess the association between MVD and overall survival(OS)or progression-free survival(PFS).Results:Eighteen eligible studies contained a total of 1707 NHL patients were included in this study.All the eligible studies were high quality studies scored>6 points.MVD was not different between NHL and control(SMD=0.823,95%Cl:-0.361-2.007,P=0.173).High MVD was associated with advanced disease stage(OR=1.580,95%Cl:1.080-2.311,P=0.018)and unfavorable OS(HR=1.652,95%CI:1.354-2.014,P=0.000)but not with PFS(HR=1.349,95%CI:0.852-2.136,P=0.201).Conclusion:This meta-analysis indicated that high MVD was related to advanced disease stage and associated with unfavorable OS of NHL patients.