Round-robin test for the cell-of-origin classification of diffuse large B-cell lymphoma-a feasibility study using full slide staining

Reinke, Sarah and Richter, Julia and Fend, Falko and Feller, Alfred and Hansmann, Martin-Leo and Huettl, Katrin and Oschlies, Ilske and Ott, German and Moeller, Peter and Rosenwald, Andreas and Stein, Harald and Altenbuchinger, Michael and Spang, Rainer and Klapper, Wolfram (2018) Round-robin test for the cell-of-origin classification of diffuse large B-cell lymphoma-a feasibility study using full slide staining. VIRCHOWS ARCHIV, 473 (3). pp. 341-349. ISSN 0945-6317, 1432-2307

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Abstract

Diffuse large B-cell lymphoma (DLBCL) is subdivided by gene expression analysis (GEP) into two molecular subtypes named germinal center B-cell-like (GCB) and activated B-cell-like (ABC) after their putative cell-of-origin (COO). Determination of the COO is considered mandatory in any new-diagnosed DLBCL, not otherwise specified according to the updated WHO classification. Despite the fact that pathologists are free to choose the method for COO classification, immunohistochemical (IHC) assays are most widely used. However, to the best of our knowledge, no round-robin test to evaluate the interlaboratory variability has been published so far. Eight hematopathology laboratories participated in an interlaboratory test for COO classification of 10 DLBCL tumors using the IHC classifier comprising the expression of CD10, BCL6, and MUM1 (so-called Hans classifier). The results were compared with GEP for COO signature and, in a subset, with results obtained by image analysis. In 7/10 cases (70%), at least seven laboratories assigned a given case to the same COO subtype (one center assessed one sample as not analyzable), which was in agreement with the COO subtype determined by GEP. The results in 3/10 cases (30%) revealed discrepancies between centers and/or between IHC and GEP subtype. Whereas the CD10 staining results were highly reproducible, staining for MUM1 was inconsistent in 50% and for BCL6 in 40% of cases. Image analysis of 16 slides stained for BCL6 (N = 8) and MUM1 (N = 8) of the two cases with the highest disagreement in COO classification were in line with the score of the pathologists in 14/16 stainings analyzed (87.5%). This study describes the first round-robin test for COO subtyping in DLBCL using IHC and demonstrates that COO classification using the Hans classifier yields consistent results among experienced hematopathologists, even when variable staining protocols are used. Data from this small feasibility study need to be validated in larger cohorts.

Item Type: Article
Uncontrolled Keywords: GENE-EXPRESSION; MOLECULAR CLASSIFICATION; BIOMARKER CONSORTIUM; TISSUE MICROARRAY; IMMUNOHISTOCHEMISTRY; SURVIVAL; SUBTYPES; Diffuse large B-cell lymphoma; ABC; GCB; Cell of origin; Immunohistochemistry; Hans classifier
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner)
Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 09 Jan 2020 13:31
Last Modified: 09 Jan 2020 13:31
URI: https://pred.uni-regensburg.de/id/eprint/13981

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