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Significance Of MUM1/IRF4 Protein Expression In Follicular Lymphoma

Posted on:2012-07-06Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y HuoFull Text:PDF
GTID:2214330338965081Subject:Pathology and pathophysiology
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【Objective】Follicular lymphoma (FL) is a low grade lymphoma deprived from germinal center. FL express all the markers of germinal center B-cells, such as CD20. CD79a,CD 10 and BCL6 et al, and follicular lymphoma is characterized by the t(14;18) chromosomal translocation and BCL2 over-expression. MUM1/IRF4 is an IRF family member which extensively involve in the development of lymphoid, myeloid and dendritic cells as a critical mediator. In mature B cells MUM1/IRF4 expresses highly in post-GC cells and promotes to the differentiation of plasma cells by activating the expression of Blimp-1/PRDM1 and inhibiting the expression of BCL6. Follicular lymphoma expresses GC markers and postulated arising from GC B lymphocyte. Generally, it is believed that there is rare expression of MUM1/IRF4 in FL. But several reports showed that MUM1 expresses in part of FLs mainly in high grade FLs. In this study, we investigated the expression of MUM1/IRF4 and t(14; 18) translocation and their significances in group of FL cases from China.[Methods] 98 cases of FLs from Qilu Hospital and Tianjin Tumor Hospital of eastern China were graded according to the criterion of 2008 WHO. The expression of MUM1/IRF4 protein and other markers (CD10,Bcl-2,Bcl-6,Ki67) in 98 cases were detected using tissue microarray and immunohistochemistry. Among them, t(14;18) of 94 cases were detected using fusion probe of BCL2/IGH by FISH. Statistical analysis of the correlation between them was performed using SSPS 17.0.【Results】(1) General Characteristics:in all 98 cases, there are 51 males and 47 females, their ages range is 25-83, the median age is 59. All of 98 cases,54 were FL1-2 grades (24 of FL1 and 30 of FL2),26 FL3a and 18 FL3b. The expression of MUM1, CD10, BCL6, BCL2 and Ki67 high (≥25%) were 39.8%,62.2%,80.6%, 87.8% and 50.0% respectively;(2)MUM1 predominantly expresses in high-grade follicular lymphoma(FL14.2%, 1/24; FL226.7%,8/30; FL3a 53.8%,14/26; FL3b 88.9%,16/18), and has a significantly positive correlation with FL grades (P=0.000, r=0.628) and Ki67 index (P=0.000, r=0.473);(3) MUM1 expression has a significantly negative correlation with CD10 expression (P=0.000, r=-0.597), and no significant correlation with BCL6 and BCL2.(4) Of 94 cases,55 were positive for t(14;18) (58.5%), and FL191.7%(22/24), FL2 63.0%(17/27), FL3a 52%(13/25) and FL3b 16.7%(3/18) respectively, and have significant difference was presented between them (P=0.000 r=-0.497).(5) T(14;18) of MUM1+ cases (10/55,18.2%) were significantly less than those of MUM1- (29/39,74.4%) (P=0.000)..t(14;18) translocation has a significantly negative correlation with CD10 expression. Nevertheless, there is no significant difference between the positive and negative of BCL2 and BCL6.(6) 4 cases of t(14;18) were found in 27 CD10-MUM1+ cases (14.8%), it is significant less than CD10+MUM1- cases (38/45,78.1%) (P=0.000).【Conclusions】(1)MUM1/IRF4 expression is significant higher in high-grade follicular lymphoma than in low-grade, which indicates those cases of MUMl/IRF4-positive have a high proliferative activity, more aggressive and poor prognosis. The strong expression of MUM1/IRF4 is a helpful maker for the diagnosis of high-grade follicular lymphoma.(2)MUM1 expression has a significantly positive correlation with FL grade and Ki67 index, has a significantly negative correlation with CD10 expression, and no significant correlation with BCL6 and BCL2.(3) The positive of t(14;18) is lower than the propotion of the same classification research in abroad, t(14;18) has a significantly negative correlation with the expression of MUM1/IRF4 and Ki67, and has a significantly positive correlation with the expression of CD 10, t(14;18) indicates the good progonosis.
Keywords/Search Tags:Follicular Lymphoma, MUM1/IRF4, Tissue microarray, t(14, 18)
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