MUM1/IRF4 Is Expressed in a Subset of Follicular Lymphoma with BCL6 Translocation and Short Survival
HJ Rogers, J Bodo, T Jin, TE O'Brien, ED Hsi. Cleveland Clinic, Cleveland, OH; MetroHealth Medical Center, Cleveland, OH
Background: There is a lack of prognostic markers that predict the highly variable clinical outcomes of follicular lymphoma(FL). MUM1/IRF4 is a transcription factor of post-germinal center(GC) B lymphocytes which plays a role in terminal phases of differentiation. Normally, there is an inverse relationship between BCL6 and MUM1 expression in the GC. However, we have observed MUM1 expression in a subset of FL cases, which may have a more aggressive clinical course in terms of requirement for treatment and outcome in other data sets. We evaluated MUM1 expression in a new cohort of FL cases to further characterize their pathologic features.
Design: Tissue microarray(TMA) blocks were constructed in 44 newly diagnosed FL cases. We performed immunohistochemistry(IHC) for MUM1, CD10, BCL2 and BCL6, and interphase FISH for BCL2 and BCL6 rearrangements. IHC stains were considered positive if >20% of cells expressed the marker. Cytologic grade, clinical stage, FLIPI score and overall survival(OS) were obtained. Quantum-dot(Qdot) dual immunofluorescence(IF) for MUM1 and BCL6 was performed on a subset of MUM1 positive cases to examine the coexpression of the markers.
Results: MUM1 was expressed in 13 cases(29.5%). BCL2, CD10, and BCL6 were expressed in 100%, 89% and 91%, respectively. BCL2 and BCL6 translocations were seen in 90% and 18%, respectively. MUM1 positive cases showed higher cytologic grade than MUM1 negative cases(P=.037, Fisher's Exact). Interestingly, MUM1 expression was associated with BCL6 translocation(46.2%, P=.003, Fisher's Exact) but not with other markers. Univariate Cox regression analysis of pathologic and clinical features showed that MUM1 expression, BCL6 translocation and lack of BCL2 translocation were associated with shorter OS(hazard ratio 4.06, 7.86 and 8.05, respectively; P<.02 for each). In multivariate analysis, BCL6 and BCL2 translocations retained significance. Qdot IF stain confirmed bright coexpression of MUM1 and BCL6 in 49.2% of MUM1 positive FL cells.
Conclusions: MUM1 expression in FL was associated with higher cytologic grade, BCL6 translocation and shorter OS. Aberrant coexpression of MUM1 and BCL6 was confirmed in MUM1 positive FL cells. Although some caution may be necessary because of limited study size and heterogeneous treatment, MUM1 expression in FL may be a biologic predictor of aggressive clinical outcome in FL.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 145, Tuesday Morning