[1902] 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].

Table 1
CLASSIFICATION BY IHC ALGORITHM
ABCGCBTotal
CLASSIFICATIONABC54357
BYGCB44549
GEPUnclassifiable13316
ANALYSISTotal7151122







Conclusions: This study confirms an improved accuracy of the new immunostain algorithm for the molecular subtype classification of DLBCL, in patients treated with either CHOP or Rituxan-CHOP. Immunophenotyping significantly correlates with GEP and clinical outcome, thereby enhancing the clinical application of risk stratification in DLBCL patients.
Category: Pan-genomic/Pan-proteomic Approaches to Diseases

Monday, March 22, 2010 1:00 PM

Poster Session II # 220, Monday Afternoon

 

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