pap_Kobayash_2003 - [CANCER RESEARCH 63, 60 66, January 1,...

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[CANCER RESEARCH 63, 60–66, January 1, 2003] Microarray Reveals Differences in Both Tumors and Vascular Specific Gene Expression in de Novo CD5 1 and CD5 2 Diffuse Large B-Cell Lymphomas 1 Tohru Kobayashi, 2 Motoko Yamaguchi, Seungchan Kim, Jun Morikawa, Shoko Ogawa, Satoshi Ueno, Edward Suh, Edward Dougherty, Ilya Shmulevich, Hiroshi Shiku, 3 and Wei Zhang 2,3 The Second Department of Internal Medicine, Mie University School of Medicine, Tsu, 514-8507, Japan [T. K., M. Y., J. M., S. O., S. U., H. S.]; Cancer Genomics Core Lab, Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [I. S., W. Z.]; Department of Electrical Engineering, Texas A&M University, College Station, Texas 77840 [S. K., E. D.]; and National Human Genome Research Institute [S. K.] and Division of Computational Biology, Center for Information Technology [E. S.], NIH, Bethesda, Maryland 20892 ABSTRACT Malignant lymphoma is a heterogeneous disease with different clinical features. Among diffuse large B-cell lymphomas (DLBCLs), a unique subtype has been identified recently based on cell surface marker CD5 and clinicopathological features. These de novo CD5 1 DLBCLs account for ; 10% of all of the DLBCLs and have poorer prognosis. To addition- ally understand this subtype of DLBCLs at the molecular level and to find genes that are differentially expressed in de novo CD5 1 DLBCLs, CD5 2 DLBCLs, and mantle cell lymphomas, which also have poor prognosis, we performed gene expression profiling using cDNA microarray technology. Data from a total of 9 samples of CD5 2 DLBCLs, 11 samples of de novo CD5 1 DLBCLs, and 10 samples of mantle cell lymphomas were acquired. A series of genes were identified that distinguish these three types of lymphomas. Among DLBCL cases, integrin b 1 and/or CD36 adhesion molecules were overexpressed in most cases of CD5 1 DLBCL. An immu- nohistochemical confirmation study revealed that integrin 1 was ex- pressed on lymphoma cells, which may account for the high extranodal involvement and poor prognosis of CD5 1 DLBCLs. In contrast, CD36 was overexpressed on vascular endothelia in CD5 1 DLBCLs, although there was no difference in vascularity detected by von Wilbrand factor antibody between CD5 1 and CD5 2 DLBCLs. Those results suggest that CD5 1 and CD5 2 DLBCLs have different gene expression signatures in both tumor cells and their vascular systems. INTRODUCTION DLBCL 4 is the most common subtype of B-cell lymphoma and is heterogeneous in the clinical response to current therapy and in survival time. DLBCLs 4 are also immunophenotypically heterogene- ous; ; 10% of DLBCLs express CD5 antigen (1–3). CD5 antigen is originally considered a T-cell marker but is also found in a subset of B-cells. Among B-cell malignancies, CD5 is mainly expressed in CLL and MCL (4). It has been shown that the tumor cells from patients with Richter’s syndrome resulting from aggressive transformation of CLL express CD5 antigen (5). However, most patients with CD5 1 DLBCL have no history of lymphoproliferative disease including CLL. Thus, this type of DLBCL is considered to arise “
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pap_Kobayash_2003 - [CANCER RESEARCH 63, 60 66, January 1,...

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