A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy.
PURPOSE: Hans and coworkers previously developed an immunohistochemical algorithm with approximately 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....
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1826297500072411136 |
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| author | Choi, W Weisenburger, D Greiner, T Piris, M Banham, A Delabie, J Braziel, R Geng, H Iqbal, J Lenz, G Vose, J Hans, C Fu, K Smith, L Li, M Liu, Z Gascoyne, R Rosenwald, A Ott, G Rimsza, L Campo, E Jaffe, E Jaye, D Staudt, L Chan, W |
| author_facet | Choi, W Weisenburger, D Greiner, T Piris, M Banham, A Delabie, J Braziel, R Geng, H Iqbal, J Lenz, G Vose, J Hans, C Fu, K Smith, L Li, M Liu, Z Gascoyne, R Rosenwald, A Ott, G Rimsza, L Campo, E Jaffe, E Jaye, D Staudt, L Chan, W |
| author_sort | Choi, W |
| collection | OXFORD |
| description | PURPOSE: Hans and coworkers previously developed an immunohistochemical algorithm with approximately 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. |
| first_indexed | 2024-03-07T04:32:35Z |
| format | Journal article |
| id | oxford-uuid:ced25d2f-999a-4153-9ca6-31bcaa2a0c95 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:32:35Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:ced25d2f-999a-4153-9ca6-31bcaa2a0c952022-03-27T07:38:21ZA new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ced25d2f-999a-4153-9ca6-31bcaa2a0c95EnglishSymplectic Elements at Oxford2009Choi, WWeisenburger, DGreiner, TPiris, MBanham, ADelabie, JBraziel, RGeng, HIqbal, JLenz, GVose, JHans, CFu, KSmith, LLi, MLiu, ZGascoyne, RRosenwald, AOtt, GRimsza, LCampo, EJaffe, EJaye, DStaudt, LChan, W PURPOSE: Hans and coworkers previously developed an immunohistochemical algorithm with approximately 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. |
| spellingShingle | Choi, W Weisenburger, D Greiner, T Piris, M Banham, A Delabie, J Braziel, R Geng, H Iqbal, J Lenz, G Vose, J Hans, C Fu, K Smith, L Li, M Liu, Z Gascoyne, R Rosenwald, A Ott, G Rimsza, L Campo, E Jaffe, E Jaye, D Staudt, L Chan, W A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. |
| title | A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. |
| title_full | A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. |
| title_fullStr | A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. |
| title_full_unstemmed | A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. |
| title_short | A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. |
| title_sort | new immunostain algorithm classifies diffuse large b cell lymphoma into molecular subtypes with high accuracy |
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