CD81 Protein Is Expressed in Normal Germinal Center B-Cells and in Subtypes of Human Non-Hodgkin Lymphomas
RF Luo, S Zhao, R Tibshirani, IS Lossos, R Advani, D Gratzinger, A Wong, N Talrega, R Levy, S Levy, Y Natkunam. Stanford University, Stanford, CA; University of Miami, Miami, FL
Background: CD81 is a tetraspanin cell surface protein that regulates CD19 expression in B lymphocytes and enables hepatitis C virus infection of human cells. Using a novel statistical methodology, the CD81 gene and germinal center (GC) molecules LMO2 and BCL6 were found to be highly associated with clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL) in gene expression profiling studies. Since no data was available on the expression of its cognate protein, we undertook the characterization of CD81 protein in normal and neoplastic hematolymphoid tissues.
Design: Immunohistochemistry for CD81 was performed using a monoclonal anti-CD81 antibody (clone 1D6) on tissue microarrays of over 1000 normal and neoplastic tissues. Expression patterns of GC and non-GC markers in DLBCL were compared using hierarchical clustering algorithms. RCHOP-treated DLBCL patient biopsies (106) were interrogated with CD81 and the results were correlated with overall survival (OS) and progression free survival (PFS).
Results: CD81 protein was found in normal GC B-cells and in subtypes of non-Hodgkin lymphomas, including those occurring more frequently in patients with hepatitis C infection. Staining was infrequent in myeloma, Hodgkin lymphoma, myeloid leukemia, hematopoietic precursors in normal bone marrow, and most non-hematolymphoid tissues. There was no significant association between CD81 expression and OS or PFS (p>0.05). However, in hierarchical cluster analyses of DLBCL, CD81 protein expression aligned most closely with that of LMO2, HGAL, BCL6 and CD10.
CD81 Expression in Selected Lymphomas
|Lymphoma Subtype||Total Positive||% Positive|
|Diffuse Large B-cell||123/196||63%|
|Anaplastic Large Cell||4/8||50%|
Conclusions: CD81 protein is expressed in a GC-associated manner and is present in a subset of non-Hodgkin lymphomas including DLBCL. Although its expression as a single marker was not associated with outcome in RCHOP-treated DLBCL patients, it is an additional novel GC-associated marker that warrants further study in multi-gene models used to stratify DLBCL patients into prognostic subcategories.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 148, Tuesday Morning