Abstract
Gene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center B-cell like and activated B-cell like. This classification has prognostic significance, but GEP is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver-operating characteristic curves, obviating the need for any arbitrary method. An algorithm based on the expression of CD10, FOXP1 and BCL6 was developed that had a simpler structure than other recently proposed algorithms and 92.6% concordance with GEP. In multivariate analysis, both the International Prognostic Index and our proposed algorithm were significant independent predictors of progression-free and overall survival. In conclusion, this algorithm effectively predicts prognosis of DLBCL patients matching GEP subgroups in the era of rituximab therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 2103-2113 |
| Number of pages | 11 |
| Journal | Leukemia |
| Volume | 26 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 2012 |
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Keywords
- ABC-DLBCL
- BCL6
- CD10
- diffuse large B-cell lymphoma
- FOXP1
- GCB-DLBCL
ASJC Scopus subject areas
- Hematology
- Cancer Research
- Anesthesiology and Pain Medicine
Cite this
Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma : A report from the International DLBCL Rituximab-CHOP Consortium Program Study. / Visco, C.; Li, Y.; Xu-Monette, Z. Y.; Miranda, R. N.; Green, T. M.; Li, Y.; Tzankov, A.; Wen, W.; Liu, W. M.; Kahl, B. S.; D'Amore, E. S G; Montes-Moreno, S.; Dybkær, K.; Chiu, A.; Tam, W.; Orazi, A.; Zu, Y.; Bhagat, G.; Winter, J. N.; Wang, H. Y.; O'Neill, S.; Dunphy, C. H.; Hsi, E. D.; Zhao, X. F.; Go, R. S.; Choi, W. W L; Zhou, F.; Czader, M.; Tong, J.; Zhao, X.; Van Krieken, J. H.; Huang, Q.; Ai, W.; Etzell, J.; Ponzoni, M.; Ferreri, A. J M; Piris, M. A.; Møller, M. B.; Bueso-Ramos, C. E.; Medeiros, L. J.; Wu, L.; Young, K. H.
In: Leukemia, Vol. 26, No. 9, 09.2012, p. 2103-2113.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma
T2 - A report from the International DLBCL Rituximab-CHOP Consortium Program Study
AU - Visco, C.
AU - Li, Y.
AU - Xu-Monette, Z. Y.
AU - Miranda, R. N.
AU - Green, T. M.
AU - Li, Y.
AU - Tzankov, A.
AU - Wen, W.
AU - Liu, W. M.
AU - Kahl, B. S.
AU - D'Amore, E. S G
AU - Montes-Moreno, S.
AU - Dybkær, K.
AU - Chiu, A.
AU - Tam, W.
AU - Orazi, A.
AU - Zu, Y.
AU - Bhagat, G.
AU - Winter, J. N.
AU - Wang, H. Y.
AU - O'Neill, S.
AU - Dunphy, C. H.
AU - Hsi, E. D.
AU - Zhao, X. F.
AU - Go, R. S.
AU - Choi, W. W L
AU - Zhou, F.
AU - Czader, M.
AU - Tong, J.
AU - Zhao, X.
AU - Van Krieken, J. H.
AU - Huang, Q.
AU - Ai, W.
AU - Etzell, J.
AU - Ponzoni, M.
AU - Ferreri, A. J M
AU - Piris, M. A.
AU - Møller, M. B.
AU - Bueso-Ramos, C. E.
AU - Medeiros, L. J.
AU - Wu, L.
AU - Young, K. H.
PY - 2012/9
Y1 - 2012/9
N2 - Gene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center B-cell like and activated B-cell like. This classification has prognostic significance, but GEP is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver-operating characteristic curves, obviating the need for any arbitrary method. An algorithm based on the expression of CD10, FOXP1 and BCL6 was developed that had a simpler structure than other recently proposed algorithms and 92.6% concordance with GEP. In multivariate analysis, both the International Prognostic Index and our proposed algorithm were significant independent predictors of progression-free and overall survival. In conclusion, this algorithm effectively predicts prognosis of DLBCL patients matching GEP subgroups in the era of rituximab therapy.
AB - Gene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center B-cell like and activated B-cell like. This classification has prognostic significance, but GEP is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver-operating characteristic curves, obviating the need for any arbitrary method. An algorithm based on the expression of CD10, FOXP1 and BCL6 was developed that had a simpler structure than other recently proposed algorithms and 92.6% concordance with GEP. In multivariate analysis, both the International Prognostic Index and our proposed algorithm were significant independent predictors of progression-free and overall survival. In conclusion, this algorithm effectively predicts prognosis of DLBCL patients matching GEP subgroups in the era of rituximab therapy.
KW - ABC-DLBCL
KW - BCL6
KW - CD10
KW - diffuse large B-cell lymphoma
KW - FOXP1
KW - GCB-DLBCL
UR - http://www.scopus.com/inward/record.url?scp=84865865930&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865865930&partnerID=8YFLogxK
U2 - 10.1038/leu.2012.83
DO - 10.1038/leu.2012.83
M3 - Article
C2 - 22437443
AN - SCOPUS:84865865930
VL - 26
SP - 2103
EP - 2113
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 9
ER -