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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.

Original publication

DOI

10.1200/JCO.2009.22.7058

Type

Journal article

Journal

J Clin Oncol

Publication Date

20/11/2009

Volume

27

Pages

5573 - 5579

Keywords

Aged, Aged, 80 and over, Antibodies, Monoclonal, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Cyclophosphamide, Dose-Response Relationship, Drug, Doxorubicin, Drug Administration Schedule, Enzyme-Linked Immunosorbent Assay, Female, Genes, myc, Humans, In Situ Hybridization, Fluorescence, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Prednisone, Probability, Prognosis, Proportional Hazards Models, Proto-Oncogene Proteins c-bcl-2, Risk Assessment, Rituximab, Severity of Illness Index, Survival Analysis, Treatment Outcome, Vincristine