Validation and Application of New Immunostain Algorithm for Molecular Subtype Classification of Diffuse Large B-Cell Lymphoma (DLBCL): An International DLBCL Rituxan-CHOP Consortium Program Study
JT Malik, et al.. R-CHOP Consortium Program, Madison, WI
Background: Gene expression profiling (GEP) has identified 2 molecular subtypes of DLBCL: germinal center B-cell-like (GCB) and activated B-cell-like (ABC). A new algorithm using 5 immunostains (GCET1, CD10, BCL6, FOXP1 and MUM1) was recently developed (CCR 2009;15:5494). It has yet to be independently validated in a large series of DLBCL patients treated with either CHOP or Rituxan-CHOP.
Design: The purpose of this study is to validate the new algorithm in 315 CHOP treated and 651 Rituxan-CHOP treated DLBCL patients from 20 medical centers, and to correlate with GEP and clinical outcome. Immunostains are performed on tissue microarrays, and semi-quantitative assessments are conducted using the established cut-off values to classify as either GCB or ABC. GEP is performed using U133plus 2 GeneChips (Affymetrix) method in 122 of the cases. Overall survival (OS) and event-free survival (EFS) are analyzed using the Kaplan-Meier method.
Results: Using GEP as the gold standard in 122 of the cases, 93.3% (99/106) are correctly classified into the GCB and ABC subtypes using the new algorithm [table 1]. Application of this algorithm in 315 CHOP treated DLBCL patients predicts 5-year OS (50% in GCB vs. 30% in ABC, p<0.0001) [figure 1]. Application in 651 Rituxan-CHOP treated DLBCL patients also predicts 5-year OS (60% in GCB vs. 45% in ABC, p<0.0001) [figure 2].
|CLASSIFICATION BY IHC ALGORITHM|