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Microarray Reveals Differences in Both Tumors and Vascular Specific Gene Expression in de Novo CD5⁺ and CD5^- Diffuse Large B-Cell Lymphomas¹

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

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⁺ DLBCLs account for 10% of all of the DLBCLs and have poorer prognosis. To additionally understand this subtype of DLBCLs at the molecular level and to find genes that are differentially expressed in de novo CD5⁺ DLBCLs, CD5^- 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^- DLBCLs, 11 samples of de novo CD5⁺ 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 ß1 and/or CD36 adhesion molecules were overexpressed in most cases of CD5⁺ DLBCL. An immunohistochemical confirmation study revealed that integrin ß1 was expressed on lymphoma cells, which may account for the high extranodal involvement and poor prognosis of CD5⁺ DLBCLs. In contrast, CD36 was overexpressed on vascular endothelia in CD5⁺ DLBCLs, although there was no difference in vascularity detected by von Wilbrand factor antibody between CD5⁺ and CD5^- DLBCLs. Those results suggest that CD5⁺ and CD5^- DLBCLs have different gene expression signatures in both tumor cells and their vascular systems.

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