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Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell
Lluís Colomo1, Armando López-Guillermo, María Perales
1Department of Pathology, Hospital Clínic, Institut de Recerca Biomèdica August Pi i Sunyer, University of Barcelona, Spain.
Insights
Immunophenotyping profiles in diffuse large B-cell lymphoma (DLBCL) correlate with clinicopathological features but do not predict patient outcomes. However, bcl-2 expression is linked to advanced stage and poorer overall survival (OS).
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous non-Hodgkin lymphoma.
- Immunophenotyping is crucial for classifying DLBCL subtypes.
- Understanding the relationship between immunophenotype, clinicopathological features, and patient outcomes is essential for treatment stratification.
Purpose of the Study:
- To investigate the association between immunophenotyping profiles and clinicopathological characteristics in DLBCL patients.
- To determine if immunophenotyping profiles can predict treatment response and overall survival (OS) in DLBCL.
- To evaluate the prognostic significance of bcl-2 expression in DLBCL.
Main Methods:
- Immunohistochemical analysis of 128 de novo DLBCL patients using antibodies against CD20, CD79a, CD5, CD10, bcl-6, MUM1, CD138, bcl-2, p53, p27, and Ki-67.
- Classification of patients into four immunophenotyping profiles: germinal center-CD10(+) (GC-CD10(+)), germinal center-CD10(-) (GC-CD10(-)), post-germinal center (pGC), and plasmablastic.
- Polymerase chain reaction (PCR) for bcl-2 rearrangement in 57 patients; correlation with clinicopathological features and outcomes.
Main Results:
- The pGC profile was associated with nodal presentation and immunoblastic morphology.
- GC-CD10(+) tumors showed disseminated disease, centroblastic morphology, bcl-2 rearrangement, and lower Ki-67 index.
- GC-CD10(-) patients had a higher incidence of extranodal origin, early stage, normal LDH, and lower IPI scores.
- No significant difference in response or OS was observed based on differentiation profiles.
- bcl-2 expression correlated with advanced stage, high IPI, and poor OS, maintaining its predictive value in multivariate analysis.
Conclusions:
- DLBCL immunophenotyping profiles are associated with specific clinicopathological features.
- Differentiation profiles alone are not sufficient to predict outcome in DLBCL.
- bcl-2 expression is a significant independent predictor of poor overall survival in DLBCL patients.
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.
