The Nuclear Factor-Kappa B Pathway: A Role in Primary Cutaneous Marginal Zone B-Cell Lymphomas?
MC Patel, S Bhagavathi, S Warren, M Amin, RK Malhotra, AM Blenc. William Beaumont Hospital, Royal Oak, MI; Indiana University, Indianapolis, IN
Background: Nuclear factor-kappaB (NF-kB) is a family of transcription factors that are required for T- and B-cell development, proliferation, and survival. Constitutive expression of the NF-kB signaling pathway has been recognized as a critical pathogenetic factor in lymphoma, including Hodgkin lymphoma and a variety of T- and B-cell non-Hodgkin lymphomas. Current experimental and preclinical data has shown the NF-kB pathway to be a promising therapeutic target. However, little is known about the role of NF-kB in primary cutaneous marginal zone B-cell lymphomas (PCMZL). The aim of this study is to examine the role of NF-kB activation in previously classified PCMZL and also evaluate the expression of BCL-10, an NF-kB protein activator which is aberrantly expressed in extranodal marginal zone lymphomas, particularly those with t(1;14)(p22;q32) or t(11;18)(q21;q21).
Design: We evaluated ten cases of formalin fixed-paraffin embedded PCMZL, from the archives of two institutions (2000-2008). The activation of the NF-kB pathway was evaluated using an immunostain for p65 (Cell Signaling Technology, polyclonal; 1:50) and p50 (Cell Signaling Technology, 178F3; 1:300) subunits of NF-kB. All cases were scored for intensity (weak, moderate, or strong) and localization within the nucleus and/or cytoplasm. BCL-10 (Dako; 1:4000) was also examined and scored in a similar manner.
Results: Moderate to strong nuclear and cytoplasmic staining was identified for p65 in 4 out of 10 cases (40%), with the remainder showing only weak cytoplasmic staining. P50 showed only weak cytoplasmic staining, without nuclear staining in any case. All cases showed weak cytoplasmic staining for BCL-10, with no nuclear positivity.
Conclusions: Our study identified a significant proportion (40%) of PCMZL, with nuclear positivity for p65 indicative of classical NF-kB pathway activation. However, this did not correlate with p50 or BCL-10 expression in our study. It is unclear whether this is related to different antibody clones. Alternative pathways of NF-kB activation may also be present in cases negative for nuclear expression of p65 or p50. The lack of significant BCL-10 expression as demonstrated in this study suggests a diminshed role of this protein in the NF-kB pathway and supports a lower frequency of (1;14)(p22;q32) or t(11;18)(q21;q21) in PCMZL. These results are indicative of a role of NF-kB in a subset of PCMZL, warranting further evaluation in a larger series.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 141, Tuesday Morning