title: Glioma-associated oncogene homologue 3, a hedgehog transcription factor, is highly expressed in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma.
abstract: The hedgehog signaling pathway has been shown to play a pathogenic role in diffuse large B-cell lymphoma and anaplastic large cell lymphoma, but has not been assessed in classical Hodgkin lymphoma. Glioma-associated oncogene homologues 1, 2, and 3 are transcriptional effectors of the hedgehog pathway. In this study, we first used real-time quantitative polymerase chain reaction to investigate the expressions of GLI1, GLI2, and GLI3 in 3 classical Hodgkin lymphoma cell lines. GLI1 and GLI2 were variably expressed, but GLI3 was highly expressed in all cell lines. We then used immunohistochemistry to assess glioma-associated oncogene homologues 1, 2, and 3 in 39 classical Hodgkin lymphoma patient samples. Glioma-associated oncogene homologues 1 and 2 were weakly to variably expressed in a subset of classical Hodgkin lymphoma patient samples. In contrast, glioma-associated oncogene homologue 3 showed strong, uniform nuclear expression in virtually all Hodgkin/Reed-Stenberg cells. We then performed an immunohistochemical survey of glioma-associated oncogene homologue 3 expression in 13 cases of nodular lymphocyte predominant Hodgkin lymphoma and 218 non-Hodgkin lymphomas. Most other lymphoma types showed variable or no expression of glioma-associated oncogene homologue 3, with a minor subset of cases of nodular lymphocyte predominant Hodgkin lymphoma, ALK-positive and ALK-negative anaplastic large cell lymphoma, and B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma showing a glioma-associated oncogene homologue 3 staining pattern indistinguishable from classical Hodgkin lymphoma. Our data provide a rationale to further investigate the biologic significance of glioma-associated oncogene homologue 3 in classical Hodgkin lymphoma biology.
authors.affiliation: Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Wesley O
authors.initials: WO
authors.lastname: Greaves
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Singh
authors.forename: Elias
authors.initials: E
authors.lastname: Drakos
authors.forename: Kranthi
authors.initials: K
authors.lastname: Kunkalla
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sánchez-Espiridión
authors.forename: Juan F
authors.initials: JF
authors.lastname: Garcia
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Francisco
authors.initials: F
authors.lastname: Vega
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D053823:Hedgehog Proteins / Q000378:metabolism*; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
chemical_list: D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; C082593:GLI2 protein, human; C065683:GLI3 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3