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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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NEOPLASIA

Expression of the human germinal center–associated lymphoma (HGAL) protein identifies a subset of classic Hodgkin lymphoma of germinal center derivation and improved survival

Yasodha Natkunam1, Eric D. Hsi2, Patricia Aoun3, Shuchun Zhao1, Paul Elson4, Brad Pohlman4, Hina Naushad3, Martin Bast5, Ronald Levy6, and Izidore S. Lossos7,

1 Department of Pathology, Stanford University School of Medicine, CA; 2 Department of Clinical Pathology, Cleveland Clinic Foundation, OH; 3 Department of Pathology, University of Nebraska Medical Center, Omaha; 4 Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Foundation, OH; 5 Department of Medicine, University of Nebraska, Medical Center, Omaha; 6 Department of Medicine, Division of Oncology, Stanford University School of Medicine, CA; 7 Department of Medicine, Division of Hematology-Oncology and Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami, FL

The human germinal-center–associated lymphoma (HGAL) gene and its cognate protein are expressed in a germinal center (GC)–specific manner. Its expression in classic 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 Epstein-Barr virus (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 (less than 45 years, P < .001), low stage (stage I and II, P = .04), and low International Prognostic Score (P = .002). In univariate analysis, HGAL expression was associated with improved OS (P = .01) and failure-free survival (FFS) (P = .05) but was not independent of other factors in multivariate analysis of OS or FFS. The expression of the GC-specific marker HGAL in a subset of cHL suggests that these cHLs 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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