Prognostic Significance of Diffuse Large B-Cell Lymphoma Cell of Origin Determined by Digital Gene Expression in Formalin-Fixed Paraffin-Embedded Tissue Biopsies

To evaluate the prognostic impact of cell-of-origin (COO) subgroups, assigned using the recently described gene expression-based Lymph2Cx assay in comparison with International Prognostic Index (IPI) score and MYC/BCL2 coexpression status (dual expressers). Reproducibility of COO assignment using th...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of clinical oncology Jg. 33; H. 26; S. 2848
Hauptverfasser: Scott, David W, Mottok, Anja, Ennishi, Daisuke, Wright, George W, Farinha, Pedro, Ben-Neriah, Susana, Kridel, Robert, Barry, Garrett S, Hother, Christoffer, Abrisqueta, Pau, Boyle, Merrill, Meissner, Barbara, Telenius, Adele, Savage, Kerry J, Sehn, Laurie H, Slack, Graham W, Steidl, Christian, Staudt, Louis M, Connors, Joseph M, Rimsza, Lisa M, Gascoyne, Randy D
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 10.09.2015
Schlagworte:
Adolescent
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Murine-Derived - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biopsy
Cyclophosphamide - therapeutic use
Doxorubicin - therapeutic use
Female
Gene Expression
Humans
Lymphoma, Large B-Cell, Diffuse - chemistry
Lymphoma, Large B-Cell, Diffuse - drug therapy
Lymphoma, Large B-Cell, Diffuse - mortality
Lymphoma, Large B-Cell, Diffuse - pathology
Male
Middle Aged
Paraffin Embedding
Prednisone - therapeutic use
Prognosis
Proto-Oncogene Proteins c-bcl-2 - analysis
Proto-Oncogene Proteins c-myc - analysis
Tissue Array Analysis
Vincristine - therapeutic use
ISSN:1527-7755, 1527-7755
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:To evaluate the prognostic impact of cell-of-origin (COO) subgroups, assigned using the recently described gene expression-based Lymph2Cx assay in comparison with International Prognostic Index (IPI) score and MYC/BCL2 coexpression status (dual expressers). Reproducibility of COO assignment using the Lymph2Cx assay was tested employing repeated sampling within tumor biopsies and changes in reagent lots. The assay was then applied to pretreatment formalin-fixed paraffin-embedded tissue (FFPET) biopsies from 344 patients with de novo diffuse large B-cell lymphoma (DLBCL) uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the British Columbia Cancer Agency. MYC and BCL2 protein expression was assessed using immunohistochemistry on tissue microarrays. The Lymph2Cx assay provided concordant COO calls in 96% of 49 repeatedly sampled tumor biopsies and in 100% of 83 FFPET biopsies tested across reagent lots. Critically, no frank misclassification (activated B-cell-like DLBCL to germinal center B-cell-like DLBCL or vice versa) was observed. Patients with activated B-cell-like DLBCL had significantly inferior outcomes compared with patients with germinal center B-cell-like DLBCL (log-rank P < .001 for time to progression, progression-free survival, disease-specific survival, and overall survival). In pairwise multivariable analyses, COO was associated with outcomes independent of IPI score and MYC/BCL2 immunohistochemistry. The prognostic significance of COO was particularly evident in patients with intermediate IPI scores and the non-MYC-positive/BCL2-positive subgroup (log-rank P < .001 for time to progression). Assignment of DLBCL COO by the Lymph2Cx assay using FFPET biopsies identifies patient groups with significantly different outcomes after R-CHOP, independent of IPI score and MYC/BCL2 dual expression.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1527-7755
1527-7755
DOI:10.1200/JCO.2014.60.2383