Cell-of-origin of diffuse large B-cell lymphomas determined by the Lymph2Cx assay: better prognostic indicator than Hans algorithm

Oncotarget. 2017 Mar 28;8(13):22014-22022. doi: 10.18632/oncotarget.15782.

Abstract

Diffuse large B-cell lymphomas (DLBCLs) are clinically heterogeneous and need a biomarker that can predict the outcome of treatments accurately. To assess the prognostic significance of the cell-of-origin type for DLBCLs, we applied the Lymph2Cx assay using a NanoString gene expression platform on formalin-fixed paraffin wax-embedded pretreatment tissues obtained from 82 patients with de novo DLBCL, not otherwise specified. All patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as the first line of chemotherapy. Based on the expression levels of Bcl-6, CD10, and MUM-1 measured by immunohistochemistry, cases were subdivided into germinal center B-cell (GCB) and non-GCB types according to the Hans algorithm. NanoString assay was performed on 82 cases. The Lymph2Cx assay successfully classified 82 cases into three categories: activated B-cell (ABC), GCB, and unclassified types. The concordance rate between the Lymph2Cx assay and the Hans algorithm was 73.6%. The Lymph2Cx-defined ABC type had significantly poorer outcomes compared with the GCB type (5-year overall survival, GCB vs. ABC, 96.6% vs. 77.1%, P = 0.020; 5-year disease-free survival, GCB vs. ABC, 96.6% vs. 79.2%, P = 0.018). In contrast, no significant differences were observed in survival between the two patient subgroups with DLBCL types classified by the Hans algorithm. The Lymph2Cx assay is a robust, reliable method for predicting the outcome of patients with DLBCL treated with R-CHOP chemotherapy.

Keywords: Lymph2CX; diffuse; gene expression profiling; large B-cell; lymphoma.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology*
  • Biomarkers, Tumor / genetics*
  • Cell Lineage / genetics*
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Germinal Center / metabolism
  • Germinal Center / pathology*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Paraffin Embedding
  • Prednisone / therapeutic use
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Rituximab
  • Survival Rate
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2
  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone