title: Expression of the human germinal center-associated lymphoma (HGAL) protein identifies a subset of classic Hodgkin lymphoma of germinal center derivation and improved survival.
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.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, CA, USA.
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Natkunam
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: Patricia
authors.initials: P
authors.lastname: Aoun
authors.forename: Shuchun
authors.initials: S
authors.lastname: Zhao
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: Brad
authors.initials: B
authors.lastname: Pohlman
authors.forename: Hina
authors.initials: H
authors.lastname: Naushad
authors.forename: Martin
authors.initials: M
authors.lastname: Bast
authors.forename: Ronald
authors.initials: R
authors.lastname: Levy
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000032:analysis; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000145:classification* / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000821:virology; D006801:Humans; D050835:Interferon Regulatory Factors / Q000032:analysis; D007378:Interleukins / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D053208:Kaplan-Meier Estimate; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D015260:Neprilysin / Q000032:analysis; D000074462:Positive Regulatory Domain I-Binding Factor 1; D016016:Proportional Hazards Models; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012367:RNA, Viral / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis; D012306:Risk; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000032:analysis; D000099218:Interferon Regulatory Factor-4
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D015260:Neprilysin; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012367:RNA, Viral; D012097:Repressor Proteins; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human; C476824:GCSAM protein, human; C087042:PRDM1 protein, human