Immuno-Fluorescence In Situ Hybridization Index Predicts Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP: A GELA Study

被引:100
作者
Copie-Bergman, Christiane
Gaulard, Philippe
Leroy, Karen
Briere, Josette
Baia, Maryse
Jais, Jean-Philippe
Salles, Gilles A.
Berger, Francoise
Haioun, Corinne
Tilly, Herve
Emile, Jean-Francois
Banham, Alison H.
Mounier, Nicolas
Gisselbrecht, Christian
Feugier, Pierre
Coiffier, Bertrand
Molina, Thierry J.
机构
[1] Univ Paris 12, Fac Med, Creteil, France
[2] Univ Paris Diderot, Paris, France
[3] Hop St Louis, AP HP, St Louis, France
[4] Univ Paris 05, Paris, France
[5] Hop Hotel Dieu, AP HP, F-75181 Paris, France
[6] Hosp Civils Lyon, Lyon, France
[7] Univ Lyon 1, F-69365 Lyon, France
[8] Ctr Henri Becquerel, F-76038 Rouen, France
[9] Univ Versailles St Quentin Yvelines, EA 4340, Boulogne, France
[10] Hop Ambroise Pare, AP HP, Boulogne, France
[11] Ctr Hosp & Univ Nice, Nice, France
[12] Ctr Hosp & Univ Nancy, Nancy, France
[13] Univ Oxford, Nuffield Dept Clin Lab Sci, Oxford, England
关键词
CHEMOTHERAPY PLUS RITUXIMAB; GERMINAL CENTER PHENOTYPE; ELDERLY-PATIENTS; PROGNOSTIC IMPACT; TRANSCRIPTION FACTOR; PROTEIN EXPRESSION; TISSUE MICROARRAY; GENE; BCL6; IMPROVES;
D O I
10.1200/JCO.2009.22.7058
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Purpose To evaluate the prognostic value of cell of origin immunohistochemical markers and BCL2, BCL6, and c-MYC translocations in a homogeneous cohort of patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients and Methods Patients with CD20+ DLBCL were enrolled in the randomized LNH98-5 and 01-5B Groupe d'Etude des Lymphomes de l'Adulte trials. Paraffin-embedded tumor samples of 119 patients treated with R-CHOP were analyzed by immunohistochemistry for CD10, BCL6, MUM1/IRF4, LMO2, and forkhead box protein P1 (FOXP1) expression and for BCL2, BCL6, and c-MYC breakpoints by fluorescence in situ hybridization (FISH) on tissue microarray. Results LMO2 expression and BCL2 breakpoint were associated with the germinal center (GC) subtype defined by Hans' algorithm, respectively (P < .0001; P = .0002) whereas FOXP1 expression and BCL6 breakpoint were associated with the non-germinal center (non-GC) subtype (P = .008 and P = .0001, respectively). The immunohistochemical markers analyzed independently, GC/non-GC phenotype and BCL2 breakpoint did not predict overall survival (OS). BCL6 breakpoint was significantly associated with an unfavorable impact on OS (P = .04). Interestingly, an immunoFISH index, defined by positivity for at least two of three non-GC markers (FOXP1, MUM1/IRF4, BCL6 breakpoint) was significantly associated with a shorter 5-year OS rate (44%; 95% CI, 28 to 60 v 78%; 95% CI, 59 to 89; P = .01) which was independent (P = .04) of the age-adjusted International Prognostic Index (P = .04) in multivariate analysis. Conclusion Our study demonstrates that combining immunohistochemistry with FISH allows construction of an immunoFISH index that significantly predicts survival in elderly DLBCL patients treated with R-CHOP.
引用
收藏
页码:5573 / 5579
页数:7
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