Insulin-Like Growth Factor II m-RNA Binding Protein 3 (IMP3) Is Differentially Expressed in Lymphoid Compartments and Is a Potentially Novel Marker of Normal and Neoplastic Germinal Center B-Cells
RL King, T Pasha, MR Roullet, PJ Zhang, A Bagg. Hospital of the University of Pennsylvania, Philadelphia, PA
Background: IMP3 is a member of the insulin-like growth factor II m-RNA binding protein family of proteins that play a role in RNA trafficking and stabilization, and cell growth and migration during embryogenesis, but which are down-regulated in adult tissue. However, IMP3 has recently been shown to be overexpressed in several epithelial malignancies, with increased expression correlating with aggressive behavior. These findings implicate IMP3 as an oncofetal protein and suggest its role as a biomarker for adverse outcomes. To the best of our knowledge, there is no published literature evaluating IMP3 in normal or neoplastic lymphoid tissue. In a pilot immunohistochemical (IHC) study of normal lymphoid tissue, we observed that IMP3 expression is largely restricted to germinal center (GC) B cells.
Design: We evaluated the expression of IMP3 in a series of lymphomas, specifically to determine its utility as a potentially novel marker of those of GC origin. IHC was performed on a series of 148 (predominantly B cell) lymphomas in tandem with other pertinent IHC stains and correlated with WHO subtypes.
Results: Heterogeneous expression of IMP3 was noted among different B cell lymphomas. The strongest expression was seen in malignant cells of both classic and nodular lymphocyte predominant Hodgkin lymphoma [26/30 (87%) cases positive]. Bright expression was evident in 100% [12/12] of Burkitt lymphoma cases. Follicular lymphoma showed weak positivity in most cases [14/16 (88%)]. While all cases [27/27 (100%)] of diffuse large B cell lymphoma (DLBCL) were positive for IMP3, there was wide variability in staining intensity, which did not correlate with a proposed classification into activated B cell vs GC B cell origin, as gauged by IHC. By contrast, lower proportions (10-30%) of all other lymphoma subtypes studied (mantle cell, marginal zone, small lymphocytic, B lymphoblastic, and T cell lymphoma) were IMP3 positive.
Conclusions: This is the first study to evaluate expression of IMP3 in lymphoid tissues, revealing it to be a potentially novel GC B cell marker, with distinct intensities of expression between different GC B lymphomas. However, expression of IMP3 in DLBCL is variable and does not appear to have GC B cell phenotypic associations, at least in terms of IHC algorithms. Further studies are needed to elucidate the functional role of IMP3 in normal and neoplastic B cells.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 184, Monday Morning