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Blood, 1 January 2007, Vol. 109, No. 1, pp. 298-305.
Prepublished online as a Blood First Edition Paper on September 5, 2006; DOI 10.1182/blood-2006-04-014977.
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Submitted April 4, 2006
Accepted August 16, 2006
Expression of the human Germinal Center Associated Lymphoma (HGAL) protein identifies a subset of classical Hodgkin Lymphoma of germinal center derivation and improved survival
Yasodha Natkunam, Eric Hsi, Patricia Aoun, Shuchun Zhao, Paul Elson, Brad Pohlman, Hina Naushad, Martin Bast, Ronald Levy, and Izidore S Lossos*
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
Department of Clinical Pathology, Cleveland Clinic Foundation, Cleveland, OH, USA
Department of Pathology, University of Nebraska School of Medicine, Nebraska, USA
Department of Hematologic Oncology & Blood Disorders, Cleveland Clinic, Foundation, Cleveland, OH
Department of Medicine, University of Nebraska, USA
Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA
* Corresponding author; email: ilossos{at}med.miami.edu.
The HGAL gene and its cognate protein are expressed in a germinal center (GC)-specific manner. Its expression in classical Hodgkin lymphoma (cHL) prompted us to address whether HGAL expression could distinguish biologically distinct subgroups of cHL. Tissue microarrays from 145 patients treated with curative intent showed HGAL staining in 75% and was closely correlated with MUM1/IRF4 (92%) expression. BCL6 (26%), CD10 (0%), BCL2 (31%), Blimp1 (0.02%), and EBV (20%) showed no specific correlation; neither did phospho-STAT6, a key mediator of IL-4 and IL-13-signaling that induces HGAL and is implicated in cHL pathogenesis. In our study cohort, the 5-year overall survival (OS) correlated with young age (<45 years, p <0.001), low stage (stage I and II, p = 0.04), and low International Prognostic Score (p = 0.002). In univariate analysis, HGAL expression was associated with improved OS (p=0.01) and FFS (p=.05), but was not independent of other factors in multivariate analysis on OS or FFS. The expression of the GC-specific marker HGAL in a subset of cHL suggests that these cHL retain characteristics of GC-derived lymphomas. The association with improved OS in univariate but not multivariate analysis suggests that HGAL expression is related to known clinical parameters of improved survival.
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