Open AccessReproducibility of histologic prognostic parameters for mantle cell lymphoma: cytology, Ki67, p53 and SOX11
Author(s) -
Giorgio Alberto Croci,
Eva Hoster,
Sı́lvia Beà,
Guillem Clot,
Anna Enjuanes,
David W. Scott,
José Cabeçadas,
Luis Veloza,
Elı́as Campo,
Erik ClasenLinde,
Rashmi S. Goswami,
Lars Helgeland,
Stefano Pileri,
Grzegorz Rymkiewicz,
Sarah Reinke,
Martin Dreyling,
Wolfram Klapper
Publication year - 2020
Publication title -
virchows archiv
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.226
H-Index - 99
eISSN - 1432-2307
pISSN - 0945-6317
DOI - 10.1007/s00428-020-02750-7
Subject(s) - concordance , mantle cell lymphoma , reproducibility , medicine , biomarker , cutoff , oncology , kappa , cohort , lymphoma , risk stratification , pathology , cytology , biology , statistics , biochemistry , physics , linguistics , mathematics , philosophy , quantum mechanics
Mantle cell lymphoma (MCL) shows a clinical aggressiveness that varies from patient to patient. Despite major advances in outcomes with current immunochemotherapy, the future development of therapies requires risk stratification to tailor therapy intensity. Within the group of reference pathologists for the ongoing trials of the European MCL Network, we performed a round robin test on a tissue microarray to evaluate the reproducibility in assessing the biomarkers of outcome in MCL. Cytological subtype, Ki67-index and expression of p53 and SOX11 were evaluated on 20 diagnostic tumour samples by eight participating labs independently. We demonstrate that the assessment of the proliferation index by counting the Ki67 positive cells as well as assessment of SOX11 and p53 expression status is reproducible between labs. For the most established prognostic biomarker, Ki67, the intra-class correlation coefficient was very good when assessed as a continuous parameter (0.87). The agreement was lower when the values were analysed in a dichotomized way applying the commonly used cutoff of 30% (kappa = 0.65, complete concordance of all labs in 13/20 (65%)). Cases with discrepant results between labs in the dichotomized analysis showed mean values close to the cutoff of 30%. Centralised scoring and digital image analysis revealed results in line with the scores from individual labs. All cases in our cohort were additionally assessed for gene expression signatures and of TP53 gene alterations. Given the good reproducibility when guidelines of assessment are applied, the biomarker studied in this inter-laboratory test presents potential candidates to be enhanced for risk-stratification in the future clinical trials.