Immuno-fluorescence in situ hybridization index predicts survival in patients with diffuse large B-cell lymphoma treated with R-CHOP: a GELA study.

Journal article

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.

Authors: Copie-Bergman, C; Gaulard, P; Leroy, K; Briere, J; Baia, M

• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
• Volume: 27
• Issue: 33
• Pages: 5573-5579
• Publication date: 2009-11-01
• DOI: 10.1200/jco.2009.22.7058
• EISSN: 1527-7755
• ISSN: 0732-183X
• Language: English
• Keywords: Lymphoma, Large B-Cell, Diffuse; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Severity of Illness Index; Female; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Doxorubicin; Proportional Hazards Models; Biological Markers; In Situ Hybridization, Fluorescence; Dose-Response Relationship, Drug; Vincristine; Proto-Oncogene Proteins c-bcl-2; Aged, 80 and over; Survival Analysis; Aged; Humans; Male; Cyclophosphamide; Antibodies, Monoclonal, Murine-Derived; Prognosis; Prednisone; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Genes, myc; Antibodies, Monoclonal; Risk Assessment; Probability