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 Natkunam, Eric D. Hsi, Patricia Aoun, Shuchun Zhao, Paul Elson, Brad Pohlman, Hina Naushad, Martin Bast, Ronald Levy, Izidore Lossos

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)298-305
Number of pages8
JournalBlood
Volume109
Issue number1
DOIs
StatePublished - Jan 1 2007

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Germinal Center
Hodgkin Disease
Lymphoma
Survival
Interleukin-13
Microarrays
Viruses
Interleukin-4
Genes
Association reactions
Tissue
Proteins
Multivariate Analysis
human GCET2 protein
Human Herpesvirus 4
Cohort Studies
Staining and Labeling

ASJC Scopus subject areas

  • Hematology

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Expression of the human germinal center-associated lymphoma (HGAL) protein identifies a subset of classic Hodgkin lymphoma of germinal center derivation and improved survival. / Natkunam, Yasodha; Hsi, Eric D.; Aoun, Patricia; Zhao, Shuchun; Elson, Paul; Pohlman, Brad; Naushad, Hina; Bast, Martin; Levy, Ronald; Lossos, Izidore.

In: Blood, Vol. 109, No. 1, 01.01.2007, p. 298-305.

Research output: Contribution to journalArticle

Natkunam, Yasodha ; Hsi, Eric D. ; Aoun, Patricia ; Zhao, Shuchun ; Elson, Paul ; Pohlman, Brad ; Naushad, Hina ; Bast, Martin ; Levy, Ronald ; Lossos, Izidore. / Expression of the human germinal center-associated lymphoma (HGAL) protein identifies a subset of classic Hodgkin lymphoma of germinal center derivation and improved survival. In: Blood. 2007 ; Vol. 109, No. 1. pp. 298-305.
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abstract = "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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AU - Zhao, Shuchun

AU - Elson, Paul

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