Zeta-associated protein-70 ( ZAP-70), mostly assessed by flow-cytometry ( FC), recently emerged as reliable prognostic factor in chronic lymphocytic leukaemia ( CLL) at presentation. We evaluated ZAP-70 expression in 156 CLL patients by immunohistochemistry ( IHC) on formalin-fixed bone marrow ( BM) biopsies at diagnosis. At presentation, 117 patients ( 75%) were with Binet stage A, 27 ( 17%) stage B and 12 ( 8%) stage C. Median follow-up was 61 months ( range 6 - 242). ZAP-70 was expressed in neoplastic lymphocytes of 69 patients ( 44%). Concordance between ZAP-70 by IHC and ZAP-70 by FC, immunoglobulin heavy chain variable genes ( IGHV) mutational status and CD38 expression was found in 41/46 ( 89%), 41/49 ( 80%) and in 60/88 ( 68%) tested cases, respectively. ZAP-70 expression significantly correlated with advanced Binet stage ( B - C), diffuse BM infiltration, increased lactate dehydrogenase ( LDH) and beta 2-microglobulin serum levels and lymphocyte doubling time < 12 months. ZAP-70 positivity was significantly related to poorer time to progression ( median 16 months vs 158 of ZAP-70-negative cases) ( P < 0.0001) and overall survival ( median 106 months vs not reached) ( P = 0.0002); this correlation was confirmed at multivariate analysis. ZAP-70 expression correlated with poorer outcome also when evaluated only in the 117 stage A patients. In conclusion, immunohistological detection of ZAP-70 on formalin-fixed BM biopsies at diagnosis appears a useful methodological approach to identify patients with poor prognosis in CLL.

ZAP-70 expression, as detected by immunohistochemistry on bone marrow biopsies from early-phase CLL patients, is a strong adverse prognostic factor

GHIA , PAOLO PROSPERO;
2007-01-01

Abstract

Zeta-associated protein-70 ( ZAP-70), mostly assessed by flow-cytometry ( FC), recently emerged as reliable prognostic factor in chronic lymphocytic leukaemia ( CLL) at presentation. We evaluated ZAP-70 expression in 156 CLL patients by immunohistochemistry ( IHC) on formalin-fixed bone marrow ( BM) biopsies at diagnosis. At presentation, 117 patients ( 75%) were with Binet stage A, 27 ( 17%) stage B and 12 ( 8%) stage C. Median follow-up was 61 months ( range 6 - 242). ZAP-70 was expressed in neoplastic lymphocytes of 69 patients ( 44%). Concordance between ZAP-70 by IHC and ZAP-70 by FC, immunoglobulin heavy chain variable genes ( IGHV) mutational status and CD38 expression was found in 41/46 ( 89%), 41/49 ( 80%) and in 60/88 ( 68%) tested cases, respectively. ZAP-70 expression significantly correlated with advanced Binet stage ( B - C), diffuse BM infiltration, increased lactate dehydrogenase ( LDH) and beta 2-microglobulin serum levels and lymphocyte doubling time < 12 months. ZAP-70 positivity was significantly related to poorer time to progression ( median 16 months vs 158 of ZAP-70-negative cases) ( P < 0.0001) and overall survival ( median 106 months vs not reached) ( P = 0.0002); this correlation was confirmed at multivariate analysis. ZAP-70 expression correlated with poorer outcome also when evaluated only in the 117 stage A patients. In conclusion, immunohistological detection of ZAP-70 on formalin-fixed BM biopsies at diagnosis appears a useful methodological approach to identify patients with poor prognosis in CLL.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/18002
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