HGAL, also known as Germinal Center-associated Lymphoma Protein or GCET, is an important prognostic marker for staging Lymphomas derived from germinal centers. Analysis of the GCET2 protein sequence indicated that it may be involved in signal transduction in the cytoplasm. The HGAL gene comprises 6 exons and encodes a cytoplasmic protein of 178 amino acids that contains an immunoreceptor tyrosine-based activation motif (ITAM). Two newly characterized germinal center B-cell-associated genes, GCET1 and GCET2, have differential expression in normal and neoplastic B cells. Expression of the HGAL gene is specifically induced in B cells by interleukin-4 (IL-4).

The HGAL protein has been shown to be expressed in the cytoplasm of germinal center B lymphocytes and in B cell lymphomas of germinal center derivation. HGAL is absent in Mantle and Marginal zone B-cells and in the Interfollicular and Paracortical regions in normal Tonsils and Lymph Nodes. HGAL is an ideal marker for the detection of Germinal Center-derived B-cell Lymphomas and has the highest overall sensitivity of detecting Follicular Lymphoma. HGAL has been identified in gene-expression profiling studies of Diffuse Large B-Cell Lymphoma (DLBCL). Among 727 Lymphomas tested by immunohistochemistry on tissue microarrays, HGAL staining was found in Follicular Lymphomas (103 of 107), Burkitt Lymphomas (40 of 40), Mediastinal Large B Lymphomas (7 of 8), and in DLBCLs (103 of 151). Expression of HGAL protein identifies a subset of classic Hodgkin Lymphoma of Germinal Center derivation with improved survival.