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Scheda a cura di Marco Chilosi (GYM)
BCL-2 **** NEI LINFOMI B di derivazione follicolare
_____________________________________________________________________ Follicolo normale in un linfonodo reattivo: Il mantello follicolare è invece composto da linfociti intensamente bcl-2 positivi
LINFOMA FOLLICOLARE: Intensa espressione di bcl-2 in un follicolo neoplastico. Si confronti questa immagine con l'aspetto "a bersaglio" di un follicolo iperplastico (figura precedente).
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Linfoma CB/CC diffuso. Intensa espressione di bcl-2 nelle cellule neoplastiche (sx). La componente proliferante (Ki67+) è distribuita focalmente (dx)
Utilizzazione di bcl-2 nella stadiazione dei linfomi su biopsia osteomidollare
Espressione di bcl-2 negli altri linfomi. I linfomi a basso grado di malignità esprimono elevati livelli di bcl-2, dimostrabili con metodiche immunoistologiche su materiale di routine. Questa espressione è correlata con il loro livello maturativo e NON alla presenza di traslocazione.
Linfoma B a cellule del mantello (MCL) Leucemia linfatica cronica (sono bcl-2 positivi anche i centri di replicazione)(B-CLL)
N Engl J Med 1988 Jun 23;318(25):1638-44 Expression in non-Hodgkin's lymphoma of the bcl-2 protein associated with the t(14;18) chromosomal translocation. Ngan BY, Chen-Levy Z, Weiss LM, Warnke RA, Cleary ML. Department of Pathology, Stanford University School of Medicine, CA 94305. For many non-Hodgkin's lymphomas, the bcl-2 gene has been implicated as a likely proto-oncogene, since it is consistently located at or near the breakpoint sites of t(14;18) chromosomal translocations. To define the role of the protein product of the bcl-2 gene in lymphoid cancers, we used anti-bcl-2 antibodies to perform immunohistochemical studies of frozen sections of 136 tissue specimens affected by lymphoma or non-neoplastic lymphoid disorders. Immunoreactive bcl-2 protein was observed in the neoplastic cells in almost all the follicular lymphomas, whereas no bcl-2 protein was detected in follicles affected by non-neoplastic processes or in normal lymphoid tissue. Every tumor with molecular-genetic evidence of t(14;18) translocation expressed detectable levels of bcl-2 protein, regardless of whether the breakpoint was located in or at a distance from the bcl-2 gene. These data show consistent expression of a proto-oncogenic protein in a large proportion of non-Hodgkin's lymphomas and provide further support of a role for bcl-2 in the pathogenesis of all lymphomas with the t(14;18) karyotypic abnormality. Increased expression of bcl-2 after t(14;18) translocations may be a specific marker for B-cell cancers, and demonstration of the protein with use of anti-bcl-2 antibodies could be useful in the diagnosis of many non-Hodgkin's lymphomas.
Chen CC, Raikow RB, Sonmez-Alpan E, Swerdlow SH Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania 15213-2582, USA. Immunophenotypic analysis is critical in categorizing small B-cell neoplasms; however, many recommended antibody panels have required fresh or frozen tissue. Many paraffin-reactive antibodies are now available but have been studied mostly in isolation. Therefore, the utility of a panel of paraffin-reactive antibodies in differentiating small B-cell neoplasms was investigated. Paraffin-embedded sections of small lymphocytic lymphoma/B-chronic lymphocytic leukemia (SLL/B-CLL; 12), mantle cell (MCL; 15), follicular (FL; 11), and marginal zone B-cell (MZL; eight) lymphomas were stained with CD20/L26, CD3, CD43/DF-T1 or Leu22, CD5/4C7, CD23/BU38, cyclin D1/H295, and CD10/56C6 antibodies. For select antibodies, results were compared to flow cytometric data (FC). Formalin and B5 fixation were also compared. Seven of 11 SLL/B-CLL were CD43+ CD5+ CD23+ cyclin D1- CD10-; seven of 11 MCL were CD43+ CD5+ CD23- cyclin D1+ CD10-; nine of 10 FL were CD43- CD5- CD23- cyclin D1- CD10+; and five of six MZL were CD43+ CD5- CD23- cyclin D1- CD10-. CD5, CD23, and CD10 stains showed sensitivities of 81, 88, and 100%, respectively, compared to FC. With B5 fixation, cyclin D1 was more often negative and CD5 more often equivocal. A panel of paraffin-reactive antibodies aids in classification of small B-cell neoplasms, although a small number of cases have indeterminate phenotypes and MZL have no defining features. CD5 separates most SLL/B-CLL and MCL from FL and MZL. CD23 separates SLL/B-CLL from most MCL, but cyclin D1 is most important for identifying MCL. CD10 positivity distinguishes most FL from other small B-cell lymphoid neoplasms.
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