Glioma-associated oncogene homologue 3, a hedgehog transcription factor, is highly expressed in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma

Wesley O. Greaves, Ji Eun Kim, Rajesh R. Singh, Elias Drakos, Kranthi Kunkalla, Beatriz Sánchez-Espiridión, Juan F. Garcia, L. Jeffrey Medeiros, Francisco Vega

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1643-1652
Number of pages10
JournalHuman pathology
Volume42
Issue number11
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

Keywords

  • Classical Hodgkin lymphoma
  • GLI3
  • Hedgehog signaling
  • Immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Greaves, W. O., Kim, J. E., Singh, R. R., Drakos, E., Kunkalla, K., Sánchez-Espiridión, B., Garcia, J. F., Medeiros, L. J., & Vega, F. (2011). Glioma-associated oncogene homologue 3, a hedgehog transcription factor, is highly expressed in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma. Human pathology, 42(11), 1643-1652. https://doi.org/10.1016/j.humpath.2010.12.023