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

• Published in: Human pathology 2011-11, Vol.42 (11), p.1643-1652
• Main Authors: Greaves, Wesley O., MD, Kim, Ji Eun, MD, Singh, Rajesh R., PhD, Drakos, Elias, MD, PhD, Kunkalla, Kranthi, MS, Sánchez-Espiridión, Beatriz, MS, Garcia, Juan F., MD, Medeiros, L. Jeffrey, MD, Vega, Francisco, MD, PhD
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cell Line, Tumor; Classical Hodgkin lymphoma; Gene expression; GLI3; Hedgehog Proteins - metabolism; Hedgehog signaling; Hematologic and hematopoietic diseases; Hodgkin Disease - metabolism; Hodgkin Disease - pathology; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Kinases; Kruppel-Like Transcription Factors - biosynthesis; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Ligands; Lymphocytes; Lymphoma; Lymphoma, Large-Cell, Anaplastic - metabolism; Lymphoma, Non-Hodgkin - metabolism; Medical sciences; Nerve Tissue Proteins - biosynthesis; Neurology; Nuclear Proteins - biosynthesis; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymerase chain reaction; Proteins; Real-Time Polymerase Chain Reaction; Reed-Sternberg Cells - metabolism; Signal transduction; Thymus Gland - metabolism; Transcription Factors - biosynthesis; Tumors of the nervous system. Phacomatoses; Zinc Finger Protein GLI1; Zinc Finger Protein Gli2; Zinc Finger Protein Gli3
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2010.12.023

Summary 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.