title: Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma.
abstract: To analyze the relationship between immunophenotyping profile and main clinicopathological features and outcome in diffuse large B-cell lymphoma (DLBCL), we studied 128 patients (59 men, 69 women; median age 65 years) consecutively diagnosed with de novo DLBCL in a single institution. Cells from each patient were immunostained with CD20, CD79a, CD5, CD10, bcl-6, MUM1, CD138, bcl-2, p53, p27, and Ki-67 antibodies. Four immunophenotyping profiles were distinguished according to the pattern of differentiation: germinal center-CD10(+) (GC-CD10(+); CD10(+)/Bcl-6(+)/MUM1(-)/CD138(-)), germinal center-CD10(-) (GC-CD10(-); CD10(-)/Bcl-6(+)/ MUM1(-)/CD138(-)), post-germinal center (pGC; CD10(-)/bcl-6(+/-)/ MUM1(+)/CD138(-)), and plasmablastic (CD10(-)/bcl-6(-)/MUM1(+)/CD138(+)). Rearrangement of bcl-2 was studied by polymerase chain reaction (PCR) in 57 patients. Single-antigen expression was as follows: CD5, 2%; CD10, 21%; bcl-6, 72%; MUM1, 54%; CD138, 2%; bcl-2, 59%; p53, 28%; p27, 40%. Distribution according to differentiation profiles was as follows: GC-CD10(+), 24 patients, GC-CD10-, 30 patients; pGC, 60 patients; plasmablastic, 2 patients; other patterns, 12 patients. The pGC profile was associated with primary nodal presentation and immunoblastic morphology, whereas GC-CD10(+) tumors showed disseminated disease, centroblastic morphology, bcl-2 rearrangement, and lower Ki-67 proliferative index. GC-CD10(-) patients more often presented with primary extranodal origin, early stage, normal lactic acid dehydrogenase (LDH) levels, and low or low/intermediate International Prognostic Index (IPI) scores than the others. However, no significant difference was found in terms of response or overall survival (OS) according to these profiles. Expression of bcl-2 was associated with advanced stage, high or high-intermediate IPI, and poor OS. Expression of bcl-2 maintained predictive value in multivariate analysis, with stage and LDH. In conclusion, differentiation profile was associated with particular clinicopathological features but was not essential to predicting outcome in DLBCL patients.
authors.affiliation: Department of Pathology, Hospital Clínic, Institut de Recerca Biomèdica August Pi i Sunyer, University of Barcelona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Colomo
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: María
authors.initials: M
authors.lastname: Perales
authors.forename: Susana
authors.initials: S
authors.lastname: Rives
authors.forename: Antonio
authors.initials: A
authors.lastname: Martínez
authors.forename: Francesc
authors.initials: F
authors.lastname: Bosch
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016393:Lymphoma, B-Cell / Q000145:classification / Q000276:immunology* / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000276:immunology* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2