Guest guest Posted November 2, 2006 Report Share Posted November 2, 2006 Original Article Leukemia advance online publication 2 November 2006; ZAP-70 expression, as detected by immunohistochemistry on bone marrow biopsies from early-phase CLL patients, is a strong adverse prognostic factor R Zanotti1, A Ambrosetti1, M Lestani2, P Ghia3, C Pattaro4, A Remo2, F Zanetti1, S Stella5, O Perbellini1, G Prato5, G Guida5, F Caligaris-Cappio3,5, F Menestrina2, G Pizzolo1 and M Chilosi2 1Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy 2Department of Pathology, University of Verona, Verona, Italy 3Department of Oncology, Università Vita-Salute San Raffaele and Istituto Scientifico San Raffaele, Milano, Italy 4Department of Medicine and Public Health, University of Verona, Verona, Italy 5Institute for Cancer Research and Treatment, IRCC, Candiolo e Ospedale Mauriziano 'Umberto I', Torino, Italy Correspondence: Professor A Ambrosetti, Dipartimento di Medicina Clinica e Sperimentale, Sezione di Ematologia, Università di Verona, Policlinico G.B. Rossi., Piazzale L.A. Scuro 10, 37134 Verona, Italy. Received 20 April 2006; Revised 19 September 2006; Accepted 26 September 2006; Published online 2 November 2006. 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 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. Quote Link to comment Share on other sites More sharing options...
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