Synonyms: IFR4, Interferon Regulating Factor 4, Multiple Myeloma oncogen 1
by Jan Klos
Background
Coded on by MUM1 gene located on chromosome 6. Considered to be a master regulator of B-lymphocyte differentiation involved in regulation of immune response. MUM1 protein is expressed by the cells in the light zone of germinal centers (late stages of B-cell differentiation), plasma cells, activated T cells and many other related hematolymphoid cells. The expression in B-cells appears before plasmacytoid morphology.
Staining in normal cells
Under normal conditions the immunoreactivity for MUM1 is seen in plasma cells and cells of B lineage. Present in 3-10% cells in germinal centers (late centrocytes), single cells trespassing mantle zone as well as 1-5% of cells of T lineage. The lymphocytes in mantle zone are negative.
Staining in tumors
On average 35% of all B-cell lymphomas are positive including: 100% multiple myelomas and plasmablastic lymphomas, ~50% Diffuse Large B-Cell Lymphoma (DLBCL), ~60% Marginal Zone Lymphomas, ~50% Lymphoplasmacytic Lymphoma (LPL), ~40% Chronic Lymphatic Leukemia/lymphoma (CLL), less than a quarter of all grades FL (~20% of grade I&II and 79% of grade III). Only ~20% of Burkitt lymphoma and < 10% of B-ALL are positive. No staining is reported in T-ALL cases. Closely to 100% classic Hodgkin`s lymphoma and 60-70% of PTLD cases, but only ~20% of NLPHL is positive.
Among NK/T cell and pure T-cell proliferations positivity is reported in around 80% of Anaplastic Large Cell Lymphomas (ALCL) and closely to 100% of lymphomatoid papulosis. It is also seen on average in between 50-60% of all T-cell and T/&NK cell lymphomas. There is however variation among the subtypes (i.e. angioimmunoblastic is negative). Around 10% of chloromas (myeloid sarcomas) are positive. Almost all benign nevi and high percentage of malignant melanomas (80% on average, but positivity is very rare in desmoplastic type).
Staining pattern
Staining pattern is nuclear but usually a faint cytoplasmic staining is also seen.
Control tissue
Lymphoid tissue of tonsil.
Application
- Important part of the diagnostic panel for lymphoma
- Nonspecific but sensitive marker of B-lymphoid cells undergoing transformation to plasma cells
- Identification of plasma cells in panel with other antibodies
- It is included in prognostic panel for DLBCL as a part of algorithm (Hans CP et al 2004). GCL (Germinal Cell Like) phenotype associated with better prognosis shows positive staining for at least one of GCC markers CD10/BCL6 and negative for MUM1. The ABC (Activated B Cell) phenotype has worse prognosis and is associated with CD10-/Bcl6+/- and MUM1+ phenotype in at least 30% cells.
- May help to differentiate classic Hodgkin Lymphoma (MUM1+ closely to 100%) from nodular lymphocyte predominant Hodgkin lymphoma NLPHL which is negative in more than 80%.
Nuclear positivity in malignant melanoma may lead to erroneous diagnosis in cases with limited antibody panel.
Selected references
- Chang CC1, Lorek J, Sabath DE, et al. Expression of MUM1/IRF4 correlates with clinical outcome in patients with B-cell chronic lymphocytic leukemia. Blood. 2002;100(13):4671-5.
- Chang CC, McClintock S, Cleveland RP, et al. Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma. Am J Surg Pathol. 2004 Apr;28(4):464-70. PMID: 15087665
- Hans CP1, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004 Jan 1;103(1):275-82.
- https://app.immunoquery.com
- https://www.nordiqc.org/epitope.php?id=55
- Natkunam Y, Warnke RA, Montgomery K, et al. Analysis of MUM1/IRF4 protein expression using tissue microarrays and immunohistochemistry. Mod Pathol. 2001 Jul;14(7):686-94. PMID: 11455001
- Tsuboi K1, Iida S, Inagaki H, et al. MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies. Leukemia. 2000 Mar;14(3):449-56.