PMID- 19786664 OWN - NLM STAT- MEDLINE DCOM- 20100105 LR - 20151119 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 27 IP - 33 DP - 2009 Nov 20 TI - Immuno-fluorescence in situ hybridization index predicts survival in patients with diffuse large B-cell lymphoma treated with R-CHOP: a GELA study. PG - 5573-9 LID - 10.1200/JCO.2009.22.7058 [doi] AB - 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. FAU - Copie-Bergman, Christiane AU - Copie-Bergman C AD - Assistance Publique-Hopitaux de Paris, Groupe Henri Mondor-Albert Chenevier, L'Institut National de la Sante et de la Recherche Medicale, Unite 955, Institut Mondor de Recherche Biomedicale; Universite Paris 12, Faculte de medecine, Creteil. christiane.copie@hmn.aphp.fr FAU - Gaulard, Philippe AU - Gaulard P FAU - Leroy, Karen AU - Leroy K FAU - Briere, Josette AU - Briere J FAU - Baia, Maryse AU - Baia M FAU - Jais, Jean-Philippe AU - Jais JP FAU - Salles, Gilles A AU - Salles GA FAU - Berger, Francoise AU - Berger F FAU - Haioun, Corinne AU - Haioun C FAU - Tilly, Herve AU - Tilly H FAU - Emile, Jean-Francois AU - Emile JF FAU - Banham, Alison H AU - Banham AH FAU - Mounier, Nicolas AU - Mounier N FAU - Gisselbrecht, Christian AU - Gisselbrecht C FAU - Feugier, Pierre AU - Feugier P FAU - Coiffier, Bertrand AU - Coiffier B FAU - Molina, Thierry J AU - Molina TJ LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20090928 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Murine-Derived) RN - 0 (Biomarkers) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 4F4X42SYQ6 (Rituximab) RN - 5J49Q6B70F (Vincristine) RN - 80168379AG (Doxorubicin) RN - 8N3DW7272P (Cyclophosphamide) RN - VB0R961HZT (Prednisone) RN - CHOP protocol SB - IM MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/administration & dosage/adverse effects MH - Antibodies, Monoclonal, Murine-Derived MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects MH - Biomarkers/blood MH - Cyclophosphamide MH - Dose-Response Relationship, Drug MH - Doxorubicin MH - Drug Administration Schedule MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - *Genes, myc MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lymphoma, Large B-Cell, Diffuse/drug therapy/*immunology/*mortality MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Predictive Value of Tests MH - Prednisone MH - Probability MH - Prognosis MH - Proportional Hazards Models MH - Proto-Oncogene Proteins c-bcl-2/*analysis MH - Risk Assessment MH - Rituximab MH - Severity of Illness Index MH - Survival Analysis MH - Treatment Outcome MH - Vincristine EDAT- 2009/09/30 06:00 MHDA- 2010/01/06 06:00 CRDT- 2009/09/30 06:00 PHST- 2009/09/30 06:00 [entrez] PHST- 2009/09/30 06:00 [pubmed] PHST- 2010/01/06 06:00 [medline] AID - JCO.2009.22.7058 [pii] AID - 10.1200/JCO.2009.22.7058 [doi] PST - ppublish SO - J Clin Oncol. 2009 Nov 20;27(33):5573-9. doi: 10.1200/JCO.2009.22.7058. Epub 2009 Sep 28.