A New Immunostain Algorithm Classifies Diffuse Large B-Cell Lymphoma into Molecular Subtypes with High Accuracy
By W. Choi, D. Weisenburger, T. Greiner, M. Piris, A. Banham, J. Delabie, R. Braziel, H. Geng, J. Iqbal, G. Lenz and 15 more. Clinical Cancer Research, 2009
660 citations recorded by the source corpus.
Purpose: Hans and coworkers previously developed an immunohistochemical algorithm with ∼80% concordance with the gene expression profiling (GEP) classification of diffuse large B-cell lymphoma (DLBCL) into the germinal center B-cell–like (GCB) and activated B-cell–like (ABC) subtypes. Since then, new antibodies specific to germinal center B-cells have been developed, which might improve the performance of an immunostain algorithm. Experimental Design: We studied 84 cases of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP)–treated DLBCL (47 GCB, 37 ABC) with GCET1, CD10, BCL6, MUM1, FOXP1, BCL2, MTA3, and cyclin D2 immunostains, and compared different combinations of the immunostaining results with the GEP classification. A perturbation analysis was also applied to eliminate the possible effects of interobserver or intraobserver variations. A separate set of 63 DLBCL cases treated with rituximab plus CHOP (37 GCB, 26 ABC) was used to validate the new algorithm. Results: A new algorithm using GCET1, CD10, BCL6, MUM1, and FOXP1 was derived that closely approximated the GEP classification with 93% concordance. Perturbation analysis indicated that the algorithm was robust within the range of observer variance. The new algorithm predicted 3-year overall survival of the validation set [GCB (87%) versus ABC (44%); P < 0.001], simulating the predictive power of the GEP classification. For a group of seven primary mediastinal large B-cell lymphoma, the new algorithm is a better prognostic classifier (all “GCB”) than the Hans' algorithm (two GCB, five non-GCB). Conclusion: Our new algorithm is significantly more accurate than the Hans' algorithm and will facilitate risk stratification of DLBCL patients and future DLBCL research using archival materials. (Clin Cancer Res 2009;15(17):5494–502)
Subfields: Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/b90aa4c4a057de2817522626c72753b9b5f7cda6
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Citations in the corpus
- The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. (2011, background): “A variety of immunohistochemical algorithms have been proposed to delineate these subsets in the routine clinical laboratory.(30) The difficulties in reproducibly distinguishing these subsets in the absence of GEP persuaded the WHO committee not to require their distinction in daily clinical practic”
- Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. (2012, methodology): “Unfortunately, the accuracy with which these algorithms correctly classify COO subtype or predict OS is variable among laboratories.(4,6,7) Alterations in oncogenes and tumor suppressor genes can drive the pathogenesis of DLBCL.”
- Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring (2012, background): “Relevant subsets of these gene products were validated at the protein level using IHC on large numbers of DLBCL specimens [10,11], and validated IHC panels are now used clinically.”
- Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue. (2014, methodology): “Subsequently, in an attempt to determine COO in standard practice using commonly available formalin-fixed paraffin-embedded tissue (FFPET), we and others used less precise(10) but relatively inexpensive binary immunohistochemical (IHC) methods.(11-13) Recently, the feasibility of quantitating gene e”
- Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2012, background): “Cell of origin can also be determined by IHC but published data on the prognostic effect of immunohistochemical techniques are contradictory, and it is not recommended to routinely base clinical decisions on these results [11, 12].”