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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3979-3986.
Prepublished online as a Blood First Edition Paper on January 27, 2005; DOI 10.1182/blood-2004-08-3112.
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NEOPLASIA
Expression of the human germinal center–associated lymphoma (HGAL) protein, a new marker of germinal center B-cell derivation
Yasodha Natkunam,
Izidore S. Lossos,
Behnaz Taidi,
Shuchun Zhao,
XiaoQing Lu,
Feying Ding,
Anne Sofie Hammer,
Teresa Marafioti,
Gerald E. Byrne, Jr,
Shoshana Levy,
Roger A Warnke, and
Ronald Levy
From the Department of Pathology and Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA; Division of Hematology-Oncology, Department of Medicine, Sylvester Comprehensive Cancer Center, Department of Molecular and Cellular Pharmacology and Department of Pathology, University of Miami, Miami, FL; Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark; and Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, United Kingdom.
We identified the human germinal center-associated lymphoma (HGAL) in gene-expression profiling studies of diffuse large B-cell lymphoma (DLBCL). The expression of HGAL correlated with survival in patients with DLBCL. The HGAL gene is the human homolog of M17, a mouse gene expressed specifically in normal germinal center (GC) B cells. We generated a monoclonal antibody against the HGAL protein and show that HGAL is expressed in the cytoplasm of GC lymphocytes and in lymphomas of GC derivation. Among 727 lymphomas tested by immunohistochemistry on tissue microarrays, HGAL staining was found in follicular lymphomas (103 of 107), Burkitt lymphomas (40 of 40), mediastinal large B lymphomas (7 of 8), and in DLBCLs (103 of 151). Most marginal zone lymphomas lacked HGAL staining. Lymphocyte-predominant Hodgkin lymphomas (12 of 17) and, surprisingly, classical Hodgkin lymphomas (78 of 107) were found to be positive. Hierarchical clustering of comparative immunohistologic results in DLBCLs demonstrates that the expression of HGAL is similar to 2 other GC-associated proteins, BCL6 and CD10, but different from 2 markers associated with a non-GC phenotype, MUM1/IRF4 and BCL2. The restricted expression and GC specificity of HGAL protein suggest that it may have an important role in the diagnosis of specific lymphomas, and, potentially in the identification of subtypes associated with different prognoses.
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