AP1-dependent galectin-1 expression delineates classical hodgkin and anaplastic large cell lymphomas from other lymphoid malignancies with shared molecular features.
OBJECTIVE
Galectin-1 (Gal1) is an immunomodulatory glycan-binding protein regulated by an AP1-dependent enhancer in Hodgkin Reed-Sternberg cells. We recently found that Reed-Sternberg cell Gal1 promotes the immunosuppressive T-helper 2/T-regulatory cell-skewed microenvironment in classical Hodgkin lymphoma (cHL). We sought to investigate whether the coordinate expression of activated AP1 pathway components and Gal1 serves as a diagnostic signature of cHL. In addition, because there are common signaling and survival pathways in cHL and additional non-Hodgkin lymphomas, we also evaluated whether the AP1/Gal1 signature is shared by other molecularly or morphologically related lymphomas.


METHODS
We evaluated 225 cases of primary cHL and non-Hodgkin lymphoma for evidence of a functional AP1/Gal1 signature by immunohistochemical techniques.


RESULTS
Gal1 is selectively expressed by malignant Reed-Sternberg cells in >90% of primary cHLs, and Gal1 expression is concordant with the activated AP1 component, c-Jun. In contrast, diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, and another Hodgkin-related entity, nodular lymphocyte-predominant Hodgkin lymphoma, do not express Gal1. However, anaplastic large cell lymphoma (ALCL), consistently expresses both Gal1 and its transcriptional regulator, c-Jun. The presence of activated c-Jun, indicative of functional AP1 activity, was confirmed by phospho-c-Jun immunostaining in cHL and ALCL.


CONCLUSIONS
These findings establish a functional AP1 signature that includes Gal1 expression in cHL and ALCL and suggests a common mechanism for tumor immunotolerance in these diseases. In addition, the combination of Gal1 and c-Jun serve as diagnostic biomarkers that delineate cHL and ALCL from other lymphomas with shared morphologic and/or molecular features.
Rodig
Scott J
SJ
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Ouyang
Jing
J
Juszczynski
Przemyslaw
P
Currie
Treeve
T
Law
Kenneth
K
Neuberg
Donna S
DS
Rabinovich
Gabriel A
GA
Shipp
Margaret A
MA
Kutok
Jeffery L
JL
D014408:Biomarkers, Tumor / Q000032:analysis*; D003937:Diagnosis, Differential; D037483:Galectin 1 / Q000096:biosynthesis*; D015870:Gene Expression; D006689:Hodgkin Disease / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017728:Lymphoma, Large-Cell, Anaplastic / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D037483:Galectin 1; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1