Molecular classification of primary mediastinal large B-cell lymphoma using routinely available tissue specimens

Anja Mottok, George Wright, Andreas Rosenwald, German Ott, Colleen Ramsower, Elias Campo, Rita M. Braziel, Jan Delabie, Dennis D. Weisenburger, Joo Y. Song, Wing C. Chan, James R. Cook, Kai Fu, Timothy Charles Greiner, Erlend Smeland, Harald Holte, Kerry J. Savage, Betty J. Glinsmann-Gibson, Randy D. Gascoyne, Louis M. StaudtElaine S. Jaffe, Joseph M. Connors, David W. Scott, Christian Steidl, Lisa M. Rimsza

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Primary mediastinal large B-cell lymphoma (PMBCL) is recognized as a distinct entity in the World Health Organization classification. Currently, the 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 clinicopathological diagnosis of an expert panel (frank misclassification rate, 3.8%). Furthermore, we demonstrate reproducibility of the assay with 100% concordance of subtype assignments at 2 independent laboratories. Future studies will determine Lymph3Cx’s utility for routine diagnostic purposes and therapeutic decision making.

Original languageEnglish (US)
Pages (from-to)2401-2405
Number of pages5
JournalBlood
Volume132
Issue number22
DOIs
StatePublished - Nov 29 2018

Fingerprint

B-Cell Lymphoma
Cells
Tissue
Assays
Lymphoma, Large B-Cell, Diffuse
Gene expression
Genes
Biopsy
Paraffin
Formaldehyde
Decision making
Health
Statistical Models
Transcriptome
Consensus
Decision Making
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Mottok, A., Wright, G., Rosenwald, A., Ott, G., Ramsower, C., Campo, E., ... Rimsza, L. M. (2018). Molecular classification of primary mediastinal large B-cell lymphoma using routinely available tissue specimens. Blood, 132(22), 2401-2405. https://doi.org/10.1182/blood-2018-05-851154

Molecular classification of primary mediastinal large B-cell lymphoma using routinely available tissue specimens. / Mottok, Anja; Wright, George; Rosenwald, Andreas; Ott, German; Ramsower, Colleen; Campo, Elias; Braziel, Rita M.; Delabie, Jan; Weisenburger, Dennis D.; Song, Joo Y.; Chan, Wing C.; Cook, James R.; Fu, Kai; Greiner, Timothy Charles; Smeland, Erlend; Holte, Harald; Savage, Kerry J.; Glinsmann-Gibson, Betty J.; Gascoyne, Randy D.; Staudt, Louis M.; Jaffe, Elaine S.; Connors, Joseph M.; Scott, David W.; Steidl, Christian; Rimsza, Lisa M.

In: Blood, Vol. 132, No. 22, 29.11.2018, p. 2401-2405.

Research output: Contribution to journalArticle

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, TC, Smeland, E, Holte, H, Savage, KJ, Glinsmann-Gibson, BJ, Gascoyne, RD, Staudt, LM, Jaffe, ES, Connors, JM, Scott, DW, Steidl, C & Rimsza, LM 2018, 'Molecular classification of primary mediastinal large B-cell lymphoma using routinely available tissue specimens', Blood, vol. 132, no. 22, pp. 2401-2405. https://doi.org/10.1182/blood-2018-05-851154
Mottok, Anja ; Wright, George ; Rosenwald, Andreas ; Ott, German ; Ramsower, Colleen ; Campo, Elias ; Braziel, Rita M. ; Delabie, Jan ; Weisenburger, Dennis D. ; Song, Joo Y. ; Chan, Wing C. ; Cook, James R. ; Fu, Kai ; Greiner, Timothy Charles ; Smeland, Erlend ; Holte, Harald ; Savage, Kerry J. ; Glinsmann-Gibson, Betty J. ; Gascoyne, Randy D. ; Staudt, Louis M. ; Jaffe, Elaine S. ; Connors, Joseph M. ; Scott, David W. ; Steidl, Christian ; Rimsza, Lisa M. / Molecular classification of primary mediastinal large B-cell lymphoma using routinely available tissue specimens. In: Blood. 2018 ; Vol. 132, No. 22. pp. 2401-2405.
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abstract = "Primary mediastinal large B-cell lymphoma (PMBCL) is recognized as a distinct entity in the World Health Organization classification. Currently, the 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 clinicopathological diagnosis of an expert panel (frank misclassification rate, 3.8{\%}). Furthermore, we demonstrate reproducibility of the assay with 100{\%} concordance of subtype assignments at 2 independent laboratories. Future studies will determine Lymph3Cx’s utility for routine diagnostic purposes and therapeutic decision making.",
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AU - Campo, Elias

AU - Braziel, Rita M.

AU - Delabie, Jan

AU - Weisenburger, Dennis D.

AU - Song, Joo Y.

AU - Chan, Wing C.

AU - Cook, James R.

AU - Fu, Kai

AU - Greiner, Timothy Charles

AU - Smeland, Erlend

AU - Holte, Harald

AU - Savage, Kerry J.

AU - Glinsmann-Gibson, Betty J.

AU - Gascoyne, Randy D.

AU - Staudt, Louis M.

AU - Jaffe, Elaine S.

AU - Connors, Joseph M.

AU - Scott, David W.

AU - Steidl, Christian

AU - Rimsza, Lisa M.

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