Glioma-Associated Oncogene Homologue-3 (GLI3): A Novel Marker for Classical Hodgkin Lymphoma
WO Greaves, JE Kim, K Kunkalla, LJ Medeiros, R Singh, F Vega. The University of Texas MD Anderson Cancer Center, Houston, TX; Seoul National University, Boramae Hospital, Seoul, Korea
Background: GLI1, GLI2 and GLI3 are transcriptional mediators of the Hedgehog (Hh) signaling pathway. GLI1 and GLI2 are transcriptional activators and GLI3 is considered to be a transcriptional repressor. Many studies have focused on the oncogenic role of GLI1 and GLI2. However, little is known about the expression of GLI3 in lymphomas. We surveyed the expression of GLI3 in a series of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL).
Design: The study group included 261 NHL and 55 HL. Non-HL consisted of 64 DLBCL, 14 T-cell/histiocyte-rich B-cell lymphoma (TCHRBCL), 6 primary mediastinal large B-cell lymphoma (PMBCL), 4 B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and HL (gray zone), 13 Burkitt lymphoma (BL), 27 follicular lymphoma (FL), 9 mantle cell lymphoma (MCL), 9 SLL/CLL, 8 marginal zone lymphoma (MZL), 22 ALK+ALCL, 11 ALK- ALCL, 11 PTCL, 6 AILT and 2 extranodal NK/T-cell lymphoma (NKTCL). HL cases were 41 classical (cHL) and 14 NLPHL. GLI3 was immunohistochemically assessed in tissue microarray and/or routine tissue sections. Expression was scored as negative or positive and the percentage of GLI3 positive cells was calculated by counting at least 200 tumor cells. Double immunohistochemistry labeling was performed in a subset of HL and TCHRBCL using GLI3 with CD30, CD20 or CD21. Five reactive lymph nodes were studied to assess the baseline expression of GLI3.
Results: In reactive lymph nodes, GLI3 was detected in follicular dendritic cells and endothelial cells but not in germinal center lymphocytes. In contrast with other lymphoma types, all cases of cHL showed strong GLI3 expression in virtually 100% of tumor cells (p=.0001) regardless of histologic subtype (table). In a subset of neoplasms GLI3 was variably expressed and no or rare expression was detected in cases of DLBCL, MCL, MZL, BL, SLL/CLL, PTCL, AILT and NKTCL.
Conclusions: GLI3 has a distinctive and characteristic expression pattern in cHL (strongly positive in virtually all tumor cells). GLI3 can be used as a diagnostic marker of cHL, distinguishing it from gray zone lymphoma, ALCL, TCHRBCL and NLPHL.
|cHL||NLPHL||ALK+ ALCL||ALK- ALCL||TCHRBCL||PMBCL||Gray zone|
|*GLI3||41 of 41||6 of 14||22 of 22||9 of 11||4 of 14||6 of 6||4 of 4|