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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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Submitted August 12, 2004
Accepted November 1, 2004
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 S Hammer, Teresa Marafioti, Gerald E Byrne Jr, Shoshana Levy, Roger A Warnke, and Ronald Levy
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
Division of Hematology-Oncology, Department of Medicine, Sylvester Comprehensive Cancer Center, Department of Molecular and Cellular Pharmacology, University of Miami, Miami, FL, USA
Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, United Kingdom
Department of Pathology, University of Miami, Miami, FL, USA
* Corresponding author; email: yaso{at}stanford.edu.
We identified the Human Germinal center-Associated Lymphoma (HGAL) gene in gene expression profiling studies of diffuse large B-cell lymphoma (DLBCL). The expression of the HGAL gene correlated with survival in patients with DLBCL. The HGAL gene is the human homologue of M17, a mouse gene expressed specifically in normal germinal center B cells. Here 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 (103/107), Burkitt (40/40), mediastinal large B (7/8), and in DLBCL (103/151). The majority of marginal zone lymphomas lacked HGAL staining. Lymphocyte predominant Hodgkin (12/17) and, surprisingly, classical Hodgkin (78/107) lymphomas were found to be positive. Hierarchical clustering of comparative immunohistologic results in DLBCL demonstrates that the expression of HGAL is similar to two other GC-associated proteins BCL6 and CD10, but different from two 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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