Microrna expression distinguishes between germinal center B cell‐like and activated B cell‐like subtypes of diffuse large B cell lymphoma

Abstract

Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that accounts for nearly 40% of all lymphoid tumors. This heterogeneous disease can be divided into germinal center B cell‐like (GCB) and activated B cell‐like (ABC) subtypes by gene expression and immunohistochemical profiling. Using microarray analysis on prototypic cell lines, we identified microRNAs (miR‐155, miR‐21 and miR‐221) that were more highly expressed in ABC‐type than GCB‐type cell lines. These microRNAs were over‐expressed in de novo DLBCL (n = 35), transformed DLBCL (n = 14) and follicular center lymphoma cases (n = 27) compared to normal B cells. Consistent with the cell line model, expression levels were higher in DLBCL cases with an ABC‐type immunophenotype than those that were GCB‐type (p < 0.05). Moreover, using multivariate analysis we found that expression of miR‐21 was an independent prognostic indicator in de novo DLBCL (p < 0.05). Interestingly, expression levels of both miR‐155 and miR‐21 were also higher in nonmalignant ABC than in GCB cells. As we also demonstrate that expression of microRNAs can be measured reliably from routine paraffin‐embedded biopsies of more than 8‐years‐old (p < 0.001), we suggest that microRNAs could be clinically useful molecular markers for DLBCL as well as other cancers.