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Clin Cancer Res. 2008 Jun 1;14(11):3338-44. doi: 10.1158/1078-0432.CCR-07-4709.

AP1-dependent galectin-1 expression delineates classical hodgkin and anaplastic large cell lymphomas from other lymphoid malignancies with shared molecular features.

Author information

1
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.

Abstract

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.

PMID:
18519761
DOI:
10.1158/1078-0432.CCR-07-4709
[Indexed for MEDLINE]
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