Expression of the B-Cell Proliferation Marker MUM1 by Melanocytic Lesions and Comparison with S100, gp100 (HMB45), and MelanA

Sundram, Uma; Harvell, Jeff D.; Rouse, Robert V.; Natkunam, Yasodha

doi:10.1097/01.mp.0000081726.49886.cf

Cited by 92 publications

(86 citation statements)

References 19 publications

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“…In humans, up to 95% of melanomas express MUM1/IRF4. 36,48 We examined canine oral melanomas and cutaneous melanocytomas, and none showed reactivity for antibody Mum-1p.…”

Section: Discussionmentioning

confidence: 99%

“…52 The only reported nonleukocytic human tumor expressing MUM1 is melanoma. 36,48 MUM1/IRF4 has been used as a prognostic factor in different studies. MUM1/IRF4 expression correlates with unfavorable prognosis in B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma 8,24 and probably in diffuse large B-cell lymphoma, 21,22 although other reports could not find such correlation.…”

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confidence: 99%

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Immunohistochemical Detection of Multiple Myeloma 1/Interferon Regulatory Factor 4 (MUM1/IRF-4) in Canine Plasmacytoma: Comparison with CD79a and CD20

2007

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Abstract. Multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) is involved in lymphoid cell differentiation, particularly in the production of plasma cells. We examined the immunoreactivity of mouse monoclonal antibody Mum-1p to MUM1/IRF4 and compared it with expression of CD79a and CD20 in 109 plasmacytomas in 107 dogs. Tissues had been fixed in formalin and embedded in paraffin. One hundred one of 109 (93.5%) tumors were positive for MUM1/IRF4. The staining was nuclear with weak cytoplasmic reaction. Fifty-nine of 105 (56.2%) plasmacytomas were positive for CD79a; only 21 of 108 (19.4%) cases were positive for CD20. MUM1/IRF4 staining was performed on 139 other tumors including B-and T-cell lymphomas, histiocytic proliferations, mast cell tumors, and melanocytic tumors. The only MUM1/IRF4-positive nonplasmacytic tumors were 10 B-cell lymphomas and 1 anaplastic lymphoma. We conclude the following: 1) Antibody Mum-1p is very specific for canine plasmacytomas, 2) antibody Mum-1p is superior in sensitivity and specificity to CD79a and CD20 for the identification of canine plasmacytomas in formalin-fixed, paraffin-embedded tissues, 3) canine lymphomas that express MUM1/IRF4 are few and usually of B-cell origin, 4) other canine leukocytic and melanocytic tumors do not express MUM1/IRF4, and 5) prospective studies are needed to determine whether the expression of MUM1/IRF4, particularly in lymphomas, has prognostic significance.

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“…In humans, up to 95% of melanomas express MUM1/IRF4. 36,48 We examined canine oral melanomas and cutaneous melanocytomas, and none showed reactivity for antibody Mum-1p.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Immunohistochemical Detection of Multiple Myeloma 1/Interferon Regulatory Factor 4 (MUM1/IRF-4) in Canine Plasmacytoma: Comparison with CD79a and CD20

2007

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“…IRF4 overexpression is a hallmark of the ABC type of DLBCL and MM (20,21) and is frequently used as a diagnostic and prognostic marker for these and other proliferative disorders (21)(22)(23). Chromosomal translocation and genetic mutation of IRF4 have been found in MM, peripheral T cell lymphomas (24), and chronic lymphocytic leukemia (CLL) (13,25).…”

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confidence: 99%

Interferon Regulatory Factor 4 Is Activated through c-Src-Mediated Tyrosine Phosphorylation in Virus-Transformed Cells

Ning

2013

J Virol

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Interferon regulatory factors (IRFs) are a small but important family of transcription factors in multiple facets of host defense systems and are also involved in the regulation of tumorigenesis, cell growth, differentiation, and myeloid cell development (1). Among IRFs, IRF2 (2), -4 (3), and -7 (4) have oncogenic and transforming potentials and antiapoptotic activity (3,5,6). These oncogenic IRFs all intimately interact with Epstein-Barr virus (EBV) latency programs (3, 7-10), which are associated with a variety of hematological and epithelial malignancies.IRF4, also known as multiple myeloma (MM) oncoprotein 1 (MUM1), is lymphocyte specific and is overexpressed in EBVtransformed cells (3,7,11,12), MM (13,14), and human T cell leukemia virus 1 (HTLV1)-infected cell lines and associated adult T cell lymphoma/leukemia (ATLL) (15)(16)(17)(18)(19). IRF4 overexpression is a hallmark of the ABC type of DLBCL and MM (20,21) and is frequently used as a diagnostic and prognostic marker for these and other proliferative disorders (21-23). Chromosomal translocation and genetic mutation of IRF4 have been found in MM, peripheral T cell lymphomas (24), and chronic lymphocytic leukemia (CLL) (13, 25). More recently, IRF4 was shown to be expressed in all LMP1-driven tumors in mice (26). These lines of evidence underscore the importance of IRF4 in these malignancies. However, the role of IRF4 in tumorigenesis remains to be elucidated.Importantly, we have recently identified B cell integration cluster (BIC), which encodes the oncogenic microRNA (miRNA) miR-155, as the first miRNA-encoding gene induced by IRF4 in virus-transformed cells (6). miR-155 plays important roles in innate immunity (27,28) and is the first identified oncogenic miRNA (oncomiR) that is implicated in various types of cancers, including lymphomas (29-31), breast cancer, leukemia, pancreatic cancer, and lung cancer (32,33). Like oncogenic IRFs, miR-155 is also associated with EBV latency (29,(34)(35)(36). Our findings therefore made a connection between these two pivotal players of cancer and immunity and have provided valuable insights into the interaction between viral oncogenesis and immune mechanisms governed by them. For example, both factors are crucial regulators of germinal center reaction (37, 38), which is implicated in lymphoma development and EBV latent infection (39). Furthermore, our microarray analysis shows that IRF4 regulates a pool of interesting genes in EBV-transformed cells (our unpublished data). Future pursuits on selected targets may disclose novel roles for IRF4 and broaden our knowledge in its interaction with viral oncogenesis and other associated cancers.Activation of IRFs by phosphorylation is prerequisite for their functions. Serine phosphorylation of IRF4 by the kinase ROCK2 activates IRF4, leading to interleukin 17/21 (IL-17/21) production in the autoimmune response in mice (40). However, how IRF4 is activated in cancer is an open question. Many proteins involved in signal transduction are tyrosine phosphorylated. Interestingly,...

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“…[118][119][120][121][122][123] MUM1 (multiple myeloma 1), a known hematolymphoid marker, shows positive immunostaining in nevi; in more than 90% of primary melanomas, with the exception of DM; and in 80% of metastatic melanomas. 124,125 To date, none of these have shown any significant benefit over those previously discussed.…”

Section: Melanocytic Neoplasmsmentioning

confidence: 85%

Immunohistochemistry in Dermatopathology

Ferringer

2015

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Immunohistochemistry is not a diagnostic test but a highly valuable tool that requires interpretation within a context.Objective.-To review the current status and limitations of immunohistochemistry in dermatopathology.Data Sources.-English-language literature published between 1980 and 2014.Conclusions.-Although immunohistochemistry is rarely completely specific or sensitive, it is an important adjunctive technique in dermatopathology and can be helpful in a series of diagnostic dilemmas.

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Expression of the B-Cell Proliferation Marker MUM1 by Melanocytic Lesions and Comparison with S100, gp100 (HMB45), and MelanA

Cited by 92 publications

References 19 publications

Immunohistochemical Detection of Multiple Myeloma 1/Interferon Regulatory Factor 4 (MUM1/IRF-4) in Canine Plasmacytoma: Comparison with CD79a and CD20

Immunohistochemical Detection of Multiple Myeloma 1/Interferon Regulatory Factor 4 (MUM1/IRF-4) in Canine Plasmacytoma: Comparison with CD79a and CD20

Interferon Regulatory Factor 4 Is Activated through c-Src-Mediated Tyrosine Phosphorylation in Virus-Transformed Cells

Immunohistochemistry in Dermatopathology

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