Molecular classification of primary mediastinal large B-cell lymphoma using routinely available tissue specimens.
Blood. 2018 Sep 26;:
Authors: Mottok A, Wright G, Rosenwald A, Ott G, Ramsower C, Campo E, Braziel RM, Delabie J, Weisenburger DD, Song JY, Chan WC, Cook JR, Fu K, Greiner T, Smeland E, Holte H, Savage KJ, Glinsmann-Gibson BJ, Gascoyne RD, Staudt LM, Jaffe ES, Connors JM, Scott DW, Steidl C, Rimsza LM
Primary mediastinal large B-cell lymphoma (PMBCL) is recognized as a distinct entity in the World Health Organization classification. Currently, diagnosis relies on consensus of histopathology, clinical variables and presentation, giving rise to diagnostic inaccuracy in routine practice. Previous studies have demonstrated that PMBCL can be distinguished from subtypes of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures. However, requirement of fresh-frozen biopsy material has precluded the transfer of gene expression-based assays to the clinic. Here, we developed a robust and accurate molecular classification assay (Lymph3Cx) for the distinction of PMBCL from DLBCL subtypes based on gene expression measurements in formalin-fixed, paraffin-embedded tissue. A probabilistic model accounting for classification error, comprising 58 gene features, was trained on 68 cases of PMBCL and DLBCL. Performance of the model was subsequently evaluated in an independent validation cohort of 158 cases and showed high agreement of the Lymph3Cx molecular classification with the clinico-pathological diagnosis of an expert panel (frank misclassification rate 3.8 %). Furthermore, we demonstrate reproducibility of the assay with 100 % concordance of subtype assignments at two independent laboratories. Future studies will determine Lymph3Cx's utility for routine diagnostic purposes and therapeutic decision making.
PMID: 30257882 [PubMed - as supplied by publisher]