MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies

Tsuboi, Kazuya; Iida, Shinsuke; Inagaki, Hiroshi; Kato, Miyuki; Hayami, Yoshihito; Hanamura, Ichiro; Miura, Kazuhisa; Harada, Shigenori; Kikuchi, Masahiro; Komatsu, Hirokazu; Banno, Shogo; Wakita, Atsushi; Nakamura, Shigeo; Eimoto, Tadaaki; Ueda, Ryuzo

doi:10.1038/sj.leu.2401696

Cited by 162 publications

(180 citation statements)

References 23 publications

(34 reference statements)

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“…38 It has been demonstrated that MUM.1 is expressed in the final step of intragerminal centre Bcell differentiation and in subsequent steps of B-cell maturation. [39][40][41] The high frequency of expression of MUM.1 in the HRS cells of classical Hodgkin's lymphoma in our cases, and in reported series, 38 suggests a similar phenotype between plasma cells and HRS cells, although the presence of BSAP expression in the latter is inconsistent with a final stage of differentiation that is seen in plasma cells.…”

Section: Discussionsupporting

confidence: 55%

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

et al. 2004

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Hodgkin's lymphoma can be considered in most cases a B-cell lymphoma due to the presence of potentially functional immunoglobulin (Ig) gene rearrangements in the neoplastic cells. In contrast to lymphocytepredominant Hodgkin's lymphoma, Hodgkin/Reed-Sternberg (HRS) cells from classical Hodgkin's lymphoma have low frequency of B-cell marker expression and lack Ig light and Ig heavy messenger RNA. Recent studies have shown transcription machinery deficiency in Hodgkin's lymphoma caused by an absence of the transcription factors OCT.1, OCT.2 and/or BOB.1. By using the tissue microarray technique, we have performed an immunohistochemical study of OCT.1, OCT.2 and BOB.1 in 325 classical Hodgkin's lymphoma cases. The results have been correlated with the expression of the B-cell markers CD20, CD79a, B-cell-specific activator protein (BSAP) and MUM.1, the presence of Epstein-Barr virus and the histological subtype. The percentage of CD20 and CD79a positivity was low (18 and 18%, respectively), whereas MUM.1 and BSAP were positive in the majority of cases. Considering the positive cases with independence of the intensity of staining, 62% of them expressed OCT.2, 59% OCT.1 and 37% BOB.1. Nevertheless, when we considered only the strongly positive cases, the results were similar to those previously described by others. No statistical association was found between the transcription factor expression, histological subtype and Epstein-Barr virus presence. To our knowledge, this is the largest series of classical Hodgkin's lymphoma cases in which the expression of transcription factors has been studied. We have found a notorious percentage of cases displaying weak positivity for OCT.2 and BOB.1 factors in HRS cells. We propose that other mechanisms different from the absence of transcription factors OCT.2 and BOB.1 might be involved in the control of Ig transcription and B lineage in classical Hodgkin's lymphoma.

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Section: Discussionsupporting

confidence: 55%

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

et al. 2004

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“…Staining in Ͼ20% of lesional cells was scored positive, as defined by Tsuboi et al (14). Staining localized to the plasma membrane was considered positive for CD138, and staining localized to the cytoplasm was considered positive for VS38.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Analysis of MUM1/IRF4 Protein Expression Using Tissue Microarrays and Immunohistochemistry

et al. 2001

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The gene encoding MUM1 was characterized as a possible translocation partner in chromosomal abnormalities involving a significant number of multiple myelomas. The overexpression of the MUM1 protein as a result of translocation t(6;14) (p25;q32) identified MUM1 as a putative regulatory molecule involved in B-cell differentiation and tumorigenesis. The expression of MUM1 protein in multiple myelomas supports this hypothesis. In the current study, using tissue microarray technology, we have tested the expression of the MUM1 protein in 1335 human malignancies and normal tissues. Our data show that the MUM1 protein is expressed in a wide spectrum of hematolymphoid neoplasms and in malignant melanomas but is absent in other human tumors. In addition, in tissue microarrays as well as in conventional paraffin sections, MUM1 staining was found to lack specificity in detecting plasmacytic differentiation as compared with two markers, CD138/Syndecan and VS38, commonly used in paraffin immunohistochemistry for detection of plasma cells.

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“…MUM-1/IRF4 (multiple myeloma oncogene 1/ interferon regulatory factor 4) is a lymphoid specific gene, which is a member of the interferon regulatory factor family of transcription factors (Tsuboi et al, 2000). Different studies show conflicting results regarding the prognostic value of MUM-1, with some reporting poor prognostic value (Braaten et al, 2003;Oh and Park, 2006;Sjo et al, 2007) while others failing to find any significant prognostic value (Chang et al, 2004;Hans et al, 2004;Muris et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of BCL-6, CD10, CD138 and MUM-1 Expression in Diffuse Large B-Cell Lymphoma patients: CD138 is a Marker of Poor Prognosis

Bodoor

Matalka²,

Hayajneh³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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The diffuse large B-cell lymphoma (DLBCL) encompasses two major groups of tumors with uneven survival outcomes -germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB). In the present study, we investigated the expression of GCB markers (BCL-6 and CD10) and non-GCB markers (CD138 and MUM-1) in an effort to evaluate their prognostic value. Paraffin-embedded tumor biopsies of 46 Jordanian DLBCL patients were analyzed, retrospectively, by immunohistochemistry to investigate the expression of BCL-6, CD10, CD138 and MUM-1. In addition, survival curves were calculated with reference to marker expression, age, sex and nodal involvement. Positive expression of BCL-6, CD10, CD138 and MUM-1 was shown in 78%, 61%, 39% and 91% of the cases, respectively, that of BCL-6 being associated with better overall survival (p = 0.02), whereas positive CD138 was linked with poor overall survival (p = 0.01). The expression of CD10 and MUM-1 had no impact on the overall survival. Among the clinical characteristics studied, diagnosis at an early age, nodal involvement and maleness were associated with a higher overall survival for DLBCL patients. Our results underline the importance of BCL-6 as a marker of better prognosis and CD138 as a marker of poor prognosis for DLBCL patients.

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MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies

Cited by 162 publications

References 23 publications

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

Analysis of MUM1/IRF4 Protein Expression Using Tissue Microarrays and Immunohistochemistry

Evaluation of BCL-6, CD10, CD138 and MUM-1 Expression in Diffuse Large B-Cell Lymphoma patients: CD138 is a Marker of Poor Prognosis

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