Ý nghĩa dự đoán của các biomarker hóa mô miễn dịch trong ung thư lympho tế bào B lớn lan tỏa: một nghiên cứu từ Liên minh Biomarker Lympho Lunenburg

Blood - Tập 117 - Trang 7070-7078 - 2011
Gilles Salles1, Daphne de Jong2, Wanling Xie3, Andreas Rosenwald4, Mukesh Chhanabhai5, Philippe Gaulard6, Wolfram Klapper7, Maria Calaminici8, Birgitta Sander9, Christoph Thorns10, Elias Campo11, Thierry Molina12, Abigail Lee8, Michael Pfreundschuh13, Sandra Horning14, Andrew Lister8, Laurie H. Sehn5, John Raemaekers15, Anton Hagenbeek16, Randy D. Gascoyne5
1Hospices Civils de Lyon and Université Claude Bernard Lyon-1, Lyon, France
2Netherlands Cancer Institute, Amsterdam, The Netherlands
3Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA
4Institute of Pathology, University of Würzburg, Würzburg, Germany
5Department of Pathology and Medical Oncology, BC Cancer Agency, University of British Columbia, Vancouver, BC
6Department of Pathology, Hôpital Henri Mondor, Créteil, France
7Department of Pathology, Hematopathology Section, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
8Cancer Research-UK Medical Oncology Unit, St Bartholomew's Hospital, London, United Kingdom
9Karolinska Institutet, Stockholm, Sweden
10Department of Pathology, Universitätsklinikum Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
11Hospital Clinic, University of Barcelona, Barcelona, Spain
12Université Paris-Descartes; Assistance Publique des Hôpitaux de Paris, Hôtel-Dieu, Paris, France
13Department of Internal Medicine I, University of Saarland, Homburg, Germany
14Department of Medicine, Stanford University Medical Center, Palo Alto, CA
15Department of Hematology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
16Department of Haematology, Academic Medical Center, Amsterdam, The Netherlands

Tóm tắt

Liên minh Biomarker Lympho Lunenburg (LLBC) đã đánh giá giá trị tiên đoán của các biomarker IHC trong một loạt lớn bệnh nhân mắc ung thư lympho tế bào B lớn lan tỏa (DLBCL). Dữ liệu lâm sàng và mẫu mô đã được thu thập từ 12 nghiên cứu ở châu Âu và Bắc Mỹ, với các bệnh nhân được điều trị trước hoặc sau kỷ nguyên rituximab. Sử dụng các vi mảng mô từ 1514 bệnh nhân, IHC cho BCL2, BCL6, CD5, CD10, MUM1, Ki67 và HLA-DR đã được thực hiện và đánh giá theo các quy trình đã được xác thực trước đó. Điểm cắt tối ưu dự đoán khả năng sống sót toàn bộ của bệnh nhân được điều trị trong kỷ nguyên rituximab chỉ có thể xác định cho CD5 (P = .003) và Ki67 (P = .02), trong khi các điểm cắt như vậy cho BCL2, BCL6, HLA-DR và MUM1 chỉ có thể được xác định ở những bệnh nhân không nhận rituximab. Một mô hình dự đoán cho bệnh nhân được điều trị trong kỷ nguyên rituximab đã xác định 4 nhóm rủi ro sử dụng BCL2, Ki67 và Chỉ số Dự đoán Quốc tế (IPI) với sự phân biệt tốt hơn của những bệnh nhân nguy cơ thấp. Các tương quan mới được công nhận giữa các biomarker cụ thể và IPI làm nổi bật tầm quan trọng của việc kiểm soát cẩn thận các yếu tố lâm sàng và sinh học trong các mô hình dự đoán. Những dữ liệu này cho thấy IPI vẫn là chỉ số tốt nhất hiện có ở những bệnh nhân DLBCL được điều trị bằng rituximab và hóa trị liệu.

Từ khóa


Tài liệu tham khảo

1993, A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project., N Engl J Med, 329, 987, 10.1056/NEJM199309303291402 Lossos, 2006, Prognostic biomarkers in diffuse large B-cell lymphoma., J Clin Oncol, 24, 995, 10.1200/JCO.2005.02.4786 Rosenwald, 2002, The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma., N Engl J Med, 346, 1937, 10.1056/NEJMoa012914 Lenz, 2008, Stromal gene signatures in large-B-cell lymphomas., N Engl J Med, 359, 2313, 10.1056/NEJMoa0802885 Lenz, 2008, Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways., Proc Natl Acad Sci U S A, 105, 13520, 10.1073/pnas.0804295105 Hans, 2004, Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray., Blood, 103, 275, 10.1182/blood-2003-05-1545 Colomo, 2003, Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma., Blood, 101, 78, 10.1182/blood-2002-04-1286 Zinzani, 2005, Identification of outcome predictors in diffuse large B-cell lymphoma. Immunohistochemical profiling of homogeneously treated de novo tumors with nodal presentation on tissue micro-arrays., Haematologica, 90, 341 van Imhoff, 2006, Prognostic impact of germinal center-associated proteins and chromosomal breakpoints in poor-risk diffuse large B-cell lymphoma., J Clin Oncol, 24, 4135, 10.1200/JCO.2006.05.5897 Moskowitz, 2005, Cell of origin, germinal center versus nongerminal center, determined by immunohistochemistry on tissue microarray, does not correlate with outcome in patients with relapsed and refractory DLBCL., Blood, 106, 3383, 10.1182/blood-2005-04-1603 Copie-Bergman, 2009, Immuno-fluorescence in situ hybridization index predicts survival in patients with diffuse large B-cell lymphoma treated with R-CHOP: A GELA Study., J Clin Oncol, 27, 5573, 10.1200/JCO.2009.22.7058 Barrans, 2002, Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma., Blood, 99, 1136, 10.1182/blood.V99.4.1136 Fu, 2008, Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell-like and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma., J Clin Oncol, 26, 4587, 10.1200/JCO.2007.15.9277 de Jong, 2007, Immunohistochemical prognostic markers in diffuse large B-cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications–a study from the Lunenburg Lymphoma Biomarker Consortium., J Clin Oncol, 25, 805, 10.1200/JCO.2006.09.4490 de Jong, 2009, Immunohistochemical prognostic markers in diffuse large B-cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications (a study from the Lunenburg Lymphoma Biomarker Consortium)., J Clin Pathol, 62, 128, 10.1136/jcp.2008.057257 Mounier, 2003, Rituximab plus CHOP (R-CHOP) overcomes bcl-2–associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL)., Blood, 101, 4279, 10.1182/blood-2002-11-3442 Winter, 2006, Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study., Blood, 107, 4207, 10.1182/blood-2005-10-4222 Coiffier, 2002, CHOP Chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma., N Engl J Med, 346, 235, 10.1056/NEJMoa011795 Habermann, 2006, Rituximab-CHOP versus CHOP alone or with maintenance Rituximab in older patients with diffuse large B-cell lymphoma., J Clin Oncol, 24, 3121, 10.1200/JCO.2005.05.1003 Sehn, 2005, Introduction of combined CHOP plus ituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia., J Clin Oncol, 23, 5027, 10.1200/JCO.2005.09.137 Pfreundschuh, 2006, CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group., Lancet Oncol, 7, 379, 10.1016/S1470-2045(06)70664-7 Verdonck, 2007, Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON)., Blood, 109, 2759, 10.1182/blood-2006-07-035709 Pfreundschuh, 2004, Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL., Blood, 104, 634, 10.1182/blood-2003-06-2095 Pfreundschuh, 2004, Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL., Blood, 104, 626, 10.1182/blood-2003-06-2094 Cook, 2007, Use and misuse of the receiver operating characteristic curve in risk prediction., Circulation, 115, 928, 10.1161/CIRCULATIONAHA.106.672402 Gönen, 2005, Concordance probability and discriminative power of proportional hazards regression., Biometrika, 92, 965, 10.1093/biomet/92.4.965 Research Development Core Team, 2009, R: A language and environment for statistical computing., R Foundation for Statistical Computing Iqbal, 2006, BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma., J Clin Oncol, 24, 961, 10.1200/JCO.2005.03.4264 Tagawa, 2005, Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma., Blood, 106, 1770, 10.1182/blood-2005-02-0542 Manazza, 2005, Follicular origin of a subset of CD5+ diffuse large B-cell lymphomas., Am J Clin Pathol, 124, 182, 10.1309/8EX5B9JFHPEK82BU Yamaguchi, 2008, De novo CD5+ diffuse large B-cell lymphoma: results of a detailed clinicopathological review in 120 patients., Haematologica, 93, 1195, 10.3324/haematol.12810 Ott, 2010, Immunoblastic morphology but not the immunohistochemical GCB/nonGCB classifier predicts outcome in diffuse large B-cell lymphoma in the RICOVER-60 trial of the DSHNHL., Blood, 116, 4916, 10.1182/blood-2010-03-276766 Reed, 1995, Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance., Curr Opin Oncol, 7, 541, 10.1097/00001622-199511000-00012 Letai, 2008, Diagnosing and exploiting cancer's addiction to blocks in apoptosis., Nat Rev Cancer, 8, 121, 10.1038/nrc2297 Ennishi, 2008, CD5 expression is potentially predictive of poor outcome among biomarkers in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy., Ann Oncol, 19, 1921, 10.1093/annonc/mdn392 Meyer, 2011, Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab., J Clin Oncol, 29, 200, 10.1200/JCO.2010.30.0368 Banham, 2005, Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma., Clin Cancer Res, 11, 1065, 10.1158/1078-0432.1065.11.3 Natkunam, 2008, LMO2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy with and without rituximab., J Clin Oncol, 26, 447, 10.1200/JCO.2007.13.0690 Lossos, 2003, HGAL is a novel interleukin-4-inducible gene that strongly predicts survival in diffuse large B-cell lymphoma., Blood, 101, 433, 10.1182/blood-2002-06-1931 Montes-Moreno, 2008, Gcet1 (centerin), a highly restricted marker for a subset of germinal center-derived lymphomas., Blood, 111, 351, 10.1182/blood-2007-06-094151 Choi, 2009, A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy., Clin Cancer Res, 15, 5494, 10.1158/1078-0432.CCR-09-0113 Savage, 2009, MYC gene re-arrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy., Blood, 114, 3533, 10.1182/blood-2009-05-220095 Klapper, 2008, Structural aberrations affecting the MYC locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL)., Leukemia, 22, 2226, 10.1038/leu.2008.230 Johnson, 2009, Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival., Blood, 114, 2273, 10.1182/blood-2009-03-212191 Young, 2008, Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study., Blood, 112, 3088, 10.1182/blood-2008-01-129783 Lossos, 2004, Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes., N Engl J Med, 350, 1828, 10.1056/NEJMoa032520 Jais, 2008, The expression of 16 genes related to the cell of origin and immune response predicts survival in elderly patients with diffuse large B-cell lymphoma treated with CHOP and rituximab., Leukemia, 22, 1917, 10.1038/leu.2008.188 Rimsza, 2008, Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP., Blood, 112, 3425, 10.1182/blood-2008-02-137372 Jardin, 2008, Detection of somatic quantitative genetic alterations by multiplex polymerase chain reaction for the prediction of outcome in diffuse large B-cell lymphomas., Haematologica, 93, 543, 10.3324/haematol.12251