CD44s and CD44v6 Are Predominantly Expressed in the Non-germinal Center B-Cell-like Type of Diffuse Large B-Cell Lymphomas

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of neoplasms and is characterized by aggressive progress and high mortality without treatment. A Korean nationwide survey suggested that the incidence of DLBCL among non-Hodgkin’s lymphomas is 42.7%, similar to the incidence of other studies. With intensive combination chemotherapy, 60% to 80% of patients achieve a complete remission, and 40% to 50% are cured. Therefore, it is important to identify those patients who may benefit from combination chemotherapies or intensive care. The categorization of DLBCL related to clinical outcome may help to identify groups of patients with distinct prognoses who may benefit from particular treatments. Using a complementary DNA (cDNA) microarray, DLBCL can be classified into 3 types with germinal center B-cell-like (GCB), activated B cell-like (ABC) and type 3 gene expression profiles. Hans et al. have shown that the immunohistochemical stains (CD10, Bcl-6, and MUM-1) can determine GCB and non-GCB types (ABC and type 3) of DLBCL. GCB type has a good survival rate, while non-GCB type has a poor outcome. CD44 protein is basically a cell adhesion protein associated with lymphocytic migration, homing and activation. It is encoded by a single gene containing 20 exons, 10 of which (v1v10) are variant exons inserted by alternative splicing. The CD44 variant isoforms are necessary for tumor spread and metastasis associated with poor prognoses. CD44 splice variants containing exon v6 (CD44v6) have been shown to be expressed in highgrade lymphomas with poor prognoses. The CD44 standard isoform (CD44s) is most abundant on lymphocytes and is expressed on activated lymphocytes and on aggressive lymphoma cells. These findings suggest that CD44s and CD44v6 are important mediators of lymphoma dissemination and that they are prognostic factors in the types of DLBCL. In this study, 2 types (GCB and non-GCB) of DLBCL were divided by immunohistochemistry (IHC) using a tissue microarray (TMA) platform in DLBCL. We investigated the relationships between CD44 protein expression and the clinicopathological parameters defined by the International Prognostic Index (IPI). CD44s and CD44v6 Are Predominantly Expressed in the Non-germinal Center B-Cell-like Type of Diffuse Large B-Cell Lymphomas