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

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


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.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Diagnosis, Differential
  • Galectin 1 / biosynthesis*
  • Gene Expression
  • Hodgkin Disease / diagnosis
  • Hodgkin Disease / genetics
  • Hodgkin Disease / metabolism*
  • Humans
  • Immunohistochemistry
  • Lymphoma, Large-Cell, Anaplastic / diagnosis
  • Lymphoma, Large-Cell, Anaplastic / genetics
  • Lymphoma, Large-Cell, Anaplastic / metabolism*
  • Lymphoproliferative Disorders / diagnosis
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism
  • Reed-Sternberg Cells / metabolism
  • Transcription Factor AP-1 / metabolism*


  • Biomarkers, Tumor
  • Galectin 1
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1