Clinical laboratory validation of the MCL35 assay for molecular risk stratification of mantle cell lymphoma
Tóm tắt
Mantle cell lymphoma (MCL) is a clinically heterogeneous B cell malignancy for which a variety of prognostic factors have been proposed. Previously, a digital gene expression profiling “proliferation signature” capable of risk stratifying MCL was identified and subsequently developed into a multi-analyte prognostic assay, known as the “MCL35” assay. In this study, we sought to explore the performance characteristics of the MCL35 assay in a clinical laboratory and compare results with the Ki67 proliferation marker. The results describe the clinical validation of the MCL35 assay for molecular risk stratification of MCL including accuracy, sensitivity, specificity, use in acid-decalcified bone marrow core biopsies, fixatives, lower limit of RNA input, quality metrics, and other laboratory parameters. The resulting data indicate that this is a robust technique with outstanding reproducibility. Overall, the data support the concept of molecular signatures, as assessed with digital gene expression profiling, for improved standardization and reproducibility for proliferation assessment in MCL.
Từ khóa
Tài liệu tham khảo
Cortelazzo S, Ponzoni M, Ferreri AJM, Dreyling M (2020) Mantle cell lymphoma. Crit Rev Oncol Hematol 153:103038. https://doi.org/10.1016/j.critrevonc.2020.103038
Li JY, Gaillard F, Moreau A, Harousseau JL, Laboisse C, Milpied N, Bataille R, Avet-Loiseau H (1999) Detection of translocation t(11;14)(q13;q32) in mantle cell lymphoma by fluorescence in situ hybridization. Am J Pathol 154(5):1449–1452. https://doi.org/10.1016/S0002-9440(10)65399-0
Wiestner A, Tehrani M, Chiorazzi M, Wright G, Gibellini F, Nakayama K, Liu H, Rosenwald A, Muller-Hermelink HK, Ott G, Chan WC, Greiner TC, Weisenburger DD, Vose J, Armitage JO, Gascoyne RD, Connors JM, Campo E, Montserrat E, Bosch F, Smeland EB, Kvaloy S, Holte H, Delabie J, Fisher RI, Grogan TM, Miller TP, Wilson WH, Jaffe ES, Staudt LM (2007) Point mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival. Blood 109(11):4599–4606. https://doi.org/10.1182/blood-2006-08-039859
Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC, Pfreundschuh M, Reiser M, Metzner B, Einsele H, Peter N, Jung W, Wormann B, Ludwig WD, Duhrsen U, Eimermacher H, Wandt H, Hasford J, Hiddemann W, Unterhalt M, German Low Grade Lymphoma Study G, European Mantle Cell Lymphoma N (2008) A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 111(2):558–565. https://doi.org/10.1182/blood-2007-06-095331
Hoster E, Klapper W, Hermine O, Kluin-Nelemans HC, Walewski J, van Hoof A, Trneny M, Geisler CH, Di Raimondo F, Szymczyk M, Stilgenbauer S, Thieblemont C, Hallek M, Forstpointner R, Pott C, Ribrag V, Doorduijn J, Hiddemann W, Dreyling MH, Unterhalt M (2014) Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network. J Clin Oncol 32(13):1338–1346. https://doi.org/10.1200/JCO.2013.52.2466
Determann O, Hoster E, Ott G, Wolfram Bernd H, Loddenkemper C, Leo Hansmann M, Barth TE, Unterhalt M, Hiddemann W, Dreyling M, Klapper W, European Mantle Cell Lymphoma N, the German Low Grade Lymphoma Study G (2008) Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group. Blood 111(4):2385–2387. https://doi.org/10.1182/blood-2007-10-117010
He JS, Chen X, Wei GQ, Sun J, Zheng WY, Shi JM, Wu WJ, Zhao Y, Zheng GF, Huang H, Cai Z (2019) Simplified MIPI-B prognostic stratification method can predict the outcome well-retrospective analysis of clinical characteristics and management of newly-diagnosed mantle cell lymphoma patients from China. Medicine (Baltimore) 98(1):e13741. https://doi.org/10.1097/MD.0000000000013741
Klapper W, Hoster E, Determann O, Oschlies I, van der Laak J, Berger F, Bernd HW, Cabecadas J, Campo E, Cogliatti S, Hansmann ML, Kluin PM, Kodet R, Krivolapov YA, Loddenkemper C, Stein H, Moller P, Barth TE, Muller-Hermelink K, Rosenwald A, Ott G, Pileri S, Ralfkiaer E, Rymkiewicz G, van Krieken JH, Wacker HH, Unterhalt M, Hiddemann W, Dreyling M, European MCLN (2009) Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network. J Hematop 2(2):103–111. https://doi.org/10.1007/s12308-009-0036-x
Croci GA, Hoster E, Bea S, Clot G, Enjuanes A, Scott DW, Cabecadas J, Veloza L, Campo E, Clasen-Linde E, Goswami RS, Helgeland L, Pileri S, Rymkiewicz G, Reinke S, Dreyling M, Klapper W (2020) Reproducibility of histologic prognostic parameters for mantle cell lymphoma: cytology, Ki67, p53 and SOX11. Virchows Arch 477(2):259–267. https://doi.org/10.1007/s00428-020-02750-7
Rosenwald A, Wright G, Wiestner A, Chan WC, Connors JM, Campo E, Gascoyne RD, Grogan TM, Muller-Hermelink HK, Smeland EB, Chiorazzi M, Giltnane JM, Hurt EM, Zhao H, Averett L, Henrickson S, Yang L, Powell J, Wilson WH, Jaffe ES, Simon R, Klausner RD, Montserrat E, Bosch F, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Fisher RI, Miller TP, LeBlanc M, Ott G, Kvaloy S, Holte H, Delabie J, Staudt LM (2003) The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell 3(2):185–197. https://doi.org/10.1016/s1535-6108(03)00028-x
Scott DW, Abrisqueta P, Wright GW, Slack GW, Mottok A, Villa D, Jares P, Rauert-Wunderlich H, Royo C, Clot G, Pinyol M, Boyle M, Chan FC, Braziel RM, Chan WC, Weisenburger DD, Cook JR, Greiner TC, Fu K, Ott G, Delabie J, Smeland EB, Holte H, Jaffe ES, Steidl C, Connors JM, Gascoyne RD, Rosenwald A, Staudt LM, Campo E, Rimsza LM, Lymphoma/Leukemia Molecular Profiling P (2017) New molecular assay for the proliferation signature in mantle cell lymphoma applicable to formalin-fixed paraffin-embedded biopsies. J Clin Oncol 35(15):1668–1677. https://doi.org/10.1200/JCO.2016.70.7901
Robetorye RS, Ramsower CA, Rosenthal AC, Yip TK, Wendel Spiczka AJ, Glinsmann-Gibson BJ, Rimsza LM (2019) Incorporation of digital gene expression profiling for cell-of-origin determination (Lymph2Cx testing) into the routine work-up of diffuse large B cell lymphoma. J Hematopath (Google Scholars) 12:3–10
Rauert-Wunderlich H, Mottok A, Scott DW, Rimsza LM, Ott G, Klapper W, Unterhalt M, Kluin-Nelemans HC, Hermine O, Hartmann S, Thorns C, Rymkiewicz G, Holte H, Dreyling M, Hoster E, Rosenwald A (2019) Validation of the MCL35 gene expression proliferation assay in randomized trials of the European Mantle Cell Lymphoma Network. Br J Haematol 184(4):616–624. https://doi.org/10.1111/bjh.15519
Clot G, Jares P, Gine E, Navarro A, Royo C, Pinyol M, Martin-Garcia D, Demajo S, Espinet B, Salar A, Ferrer A, Muntanola A, Aymerich M, Rauert-Wunderlich H, Jaffe ES, Connors JM, Gascoyne RD, Delabie J, Lopez-Guillermo A, Ott G, Wright GW, Staudt LM, Rosenwald A, Scott DW, Rimsza LM, Bea S, Campo E (2018) A gene signature that distinguishes conventional and leukemic nonnodal mantle cell lymphoma helps predict outcome. Blood 132(4):413–422. https://doi.org/10.1182/blood-2018-03-838136
Holte H, Beiske K, Boyle M, Trøen G, Blaker YN, Mykelbust J, Kvaløy S, Rosenwald A, Lingejærde OC, Rimsza LM, Smeland EB, Scott DW, Kolstad A (2018) The MCL35 gene expression proliferation assay predicts high-risk MCL patients in a Norwegian cohort of younger patients given intensive first line therapy. Br J Haematol 183(2):225–234