Prognostic Significance of Diffuse Large B-Cell Lymphoma Cell of Origin Determined by Digital Gene Expression in Formalin-Fixed Paraffin-Embedded Tissue Biopsies

Scott D et al, 2015 Journal of Clinical Oncology                                 

Link to abstract: http://jco.ascopubs.org/content/33/26/2848.long

Diffuse Large B-Cell Lymphoma (DLBCL) can be classified into 2 distinct subtypes depending on the stage of development of B-cells using gene expression analysis: germinal center B-cell–like (GCB) and activated B-cell–like (ABC) subtypes.  These groups have distinct biology and treatment outcome.   In adult oncology most clinicians still use International Prognostic Index (IPI) score and MYC/BCL2 co-expression status in routine practice to prognosticate, as the requirement for fresh frozen biopsies and microarray technology to determine sub-group seemed insurmountable.

In this paper the authors compared these “old-fashioned” markers to a recently described gene expression-based assay, the Lymph2Cx assay.  The Lymph2Cx assay can be applied to formalin fixed tissue and has been shown to be highly accurate and concordant in sub-group assignment between laboratories.  The authors applied the assay to pretreatment FFPE biopsies from 344 patients (>16 years) with de novo diffuse large B-cell lymphoma (DLBCL) uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the British Columbia Cancer Agency. 

*They found that patients with activated B-cell–like DLBCL had significantly inferior outcomes compared with patients with germinal center B-cell–like DLBCL and that this was independent of IPI score and MYC/BCL2 immunohistochemistry.  Could similar technology be used in children with DLBCL to prognosticate (in particular in the AYA population) and to drive trial questions?