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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-04-1286.

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Submitted May 6, 2002
Accepted July 26, 2002

Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma

Lluis Colomo, Armando Lopez-Guillermo*, Maria Perales, Susana Rives, Antonio Martinez, Francesc Bosch, Dolors Colomer, Brunangelo Falini, Emili Montserrat, and Elias Campo

Department of Pathology, Hospital Clinic, Institut de Recerca Biomedica August Pi i Sunyer, University of Barcelona, Barcelona, Spain
Department of Hematology, Hospital Clinic, Institut de Recerca Biomedica August Pi i Sunyer, University of Barcelona, Barcelona, Spain
Institute of Hematology, Policlinico Monteluce, University of Perugia, Perugia, Italy

* Corresponding author; email: alopezg{at}clinic.ub.es.

To analyze the relationship between immunophenotyping profile and main clinicopathological features and outcome in diffuse large B-cell lymphoma (DLBCL), 128 patients (59M/69F; median age 65 years) consecutively diagnosed with de novo DLBCL in a single institution were studied. All cases were immunostained with CD20, CD79a, CD5, CD10, bcl-6, MUM-1, CD138, bcl-2, p53, p27 and Ki-67 antibodies. Four different 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+). Bcl-2 rearrangement was studied by PCR in 57 cases. The single antigen expression was: CD5, 2%; CD10, 21%; bcl-6, 72%; MUM-1, 54%; CD138, 2%; bcl-2, 59%; p53, 28%; p27, 40%. The distribution according to differentiation profiles was: GC-CD10+, 24 cases (19%), GC-CD10-, 30 (24%); pGC, 60 (47.5%); plasmablastic, 2 (1.5%); other pattern, 12. 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 LDH levels and low or low-intermediate IPI than the others. However, no significant difference was found in terms of response or overall survival (OS) according to these profiles. Bcl-2 expression was associated with advanced stage, high or high-intermediate IPI and poor OS. Bcl-2 expression 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 predict outcome in DLBCL patients.


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