Clinical Validation of the Lymph3Cx Assay to Distinguish Primary Mediastinal Large B-Cell Lymphoma From Diffuse Large B-Cell Lymphoma

Abstract Introduction Primary mediastinal large B-cell lymphoma (PMLBCL) is recognized as a distinct lymphoid neoplasm. However, differentiation from diffuse large B-cell lymphoma (DLBCL) can be difficult due to the need for close clinicopathologic correlation and variability in morphology and immun...

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Bibliographic Details
Published in:American journal of clinical pathology 2019-09, Vol.152 (Supplement_1), p.S136-S136
Main Authors: Ramsower, Colleen, Yip, Tameson, Glinsmann-Gibson, Betty, Robetorye, Ryan, Rimsza, Lisa
Format: Article
Language:English
Subjects:
B-cell lymphoma
Cell differentiation
Clinical decision making
Clinical trials
Decision making
DNA probes
Gene expression
Laboratories
Lymphocytes B
Lymphoma
Mediastinum
Neoplasia
Paraffin
Ribonucleic acid
RNA
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Summary:Abstract Introduction Primary mediastinal large B-cell lymphoma (PMLBCL) is recognized as a distinct lymphoid neoplasm. However, differentiation from diffuse large B-cell lymphoma (DLBCL) can be difficult due to the need for close clinicopathologic correlation and variability in morphology and immunophenotype. In addition, a recent study identified lymphomas that share molecular and morphological features with PMBCL, yet do not involve the mediastinum. Correct classification of PMBCL may impact therapeutic decision making, increasing the demand for more accurate diagnostic methods. Recent research identified a new gene expression signature that robustly differentiated PMLBCL from DLBCL in both training and independent validation cohorts using RNA isolated from routinely available formalin-fixed, paraffin-embedded (FFPE) tissues. Methods This assay, known as the “Lymph3Cx,” utilizes the nCounter platform (NanoString Technologies, Seattle, WA) and consists of probes for 58 target genes (including both discriminatory and housekeeping genes) that can distinguish PMLBCL cases from DLBCL as well as the “cell-of-origin” subtypes of DLBCL. In the current study reported here, the Molecular Diagnostics–Arizona Laboratory (MDAZL) performed a full validation of the Lymph3Cx assay for use in our clinical diagnostic laboratory. Results Assay performance included accuracy (92.9%), precision (100%), analytical sensitivity (100 ng RNA limit of detection), analytical specificity (measures are in place to prevent interfering substances), reproducibility between technologists and technical replicates (100%), specimen stability (18 months for unstained tissue sections), and RNA Isolation Kit Utility (two kits with equal performance) in order to become the first CLIA-certified, CAP-accredited clinical diagnostics laboratory to offer a molecular assay for distinction of PMLBCL from DLBCL. Conclusion The Lymph3Cx assay will be prospectively used for evaluation of Mayo Clinic patients and for use as an integrated biomarker in clinical trials.
ISSN:0002-9173
1943-7722
DOI:10.1093/ajcp/aqz126.006