Expression of the Human Germinal Center-Associated Lymphoma (HGAL) Protein, a New Marker of Germinal Center B Cell Derivation.

We identified the Human Germinal center-Associated Lymphoma (HGAL) gene in gene expression profiling studies of diffuse large B-cell lymphoma (DLBCL). The expression of HGAL was correlated with survival of patients with this diagnosis. The HGAL gene is the human homologue of M17, a mouse gene that had been previously identified to be expressed specifically in normal germinal center B cells. Here we generated a monoclonal antibody against the HGAL protein and show that HGAL is expressed in the cytoplasm of GC-lymphocytes and in lymphomas considered to be derived from the GC. Among 718 lymphomas tested by immunohistochemistry on tissue microarrays, staining for HGAL protein was present in 97% (103/107) of follicular lymphoma, 100% (40/40) of Burkitt lymphoma, 87% (7/8) of mediastinal large B-cell lymphoma and 70% (103/151) of DLBCL. Nodal and extranodal marginal zone lymphomas lacked HGAL expression. Lymphocyte predominant Hodgkin (70%, 12/17) and, surprisingly, a majority of cases of classical Hodgkin (73%, 78/107) lymphomas were found to be positive.

Double-immunohistologic labeling experiments show that HGAL protein expression overlaps with the expression of BCL6 and CD10 proteins within GCs. Hierarchical clustering of comparative immunohistologic results in 151 cases of DLBCL demonstrates that the expression of HGAL is similar to two other GC-associated proteins BCL6 and CD10, but different from two markers associated with a non-GC phenotype, MUM1/IRF4 and BCL2. The restricted expression and GC-specificity of HGAL protein suggest that it may have an important role in the diagnosis of specific lymphomas, and, potentially in the identification of subtypes associated with different prognoses.