AP1-dependent galectin-1 expression delineates classical hodgkin and anaplastic large cell lymphomas from other lymphoid malignancies with shared molecular features.
PURPOSE: 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. EXPERIMENTAL DESIGN: 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.[1]References
- AP1-dependent galectin-1 expression delineates classical hodgkin and anaplastic large cell lymphomas from other lymphoid malignancies with shared molecular features. Rodig, S.J., Ouyang, J., Juszczynski, P., Currie, T., Law, K., Neuberg, D.S., Rabinovich, G.A., Shipp, M.A., Kutok, J.L. Clin. Cancer Res. (2008) [Pubmed]
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