title: Immunohistochemical analysis of ZAP-70 expression in B-cell lymphoid neoplasms.
abstract: ZAP-70 is a tyrosine kinase that participates in early B-cell differentiation and is a prognostic factor in chronic lymphocytic leukaemia (CLL), where it is associated with an unmutated configuration of the IgV(H) genes. In this study ZAP-70 expression was studied by immunohistochemistry in a spectrum of B-cell lymphoid neoplasms; this staining method was compared with flow cytometry, and the relationship of ZAP-70 expression to mutational status and prognosis was assessed. 242 tissue samples from 225 patients with B-cell lymphoid neoplasms arising at different maturational stages were included. Flow cytometry was performed in all CLL cases (n = 52). IgV(H) mutational status was determined in 25 CLL and 12 mantle cell lymphoma (MCL) patients. ZAP-70 was positive in 34/52 (65%) CLL, 9/31 (31%) Burkitt's lymphoma, 2/7 (29%) lymphoblastic lymphomas, 3/36 (8%) MCL, 1/23 (4%) marginal zone lymphoma, and 1/45 (2%) diffuse large B-cell lymphomas, but in none of the 19 follicular lymphomas or the 14 Hodgkin lymphomas. An identical ZAP-70 pattern was obtained in six patients with simultaneous biopsies from different sites and in 12 patients with sequential biopsies. Immunohistochemistry and flow cytometry gave identical results in 48 the 52 CLLs. All but one ZAP-70-positive CLL had IgV(H) gene in an unmutated configuration, whereas all but one ZAP-70-negative CLL had somatically hypermutated IgV(H). The 12 MCLs analysed were ZAP-70 negative regardless of IgV(H) mutational status (4 mutated, 8 unmutated). ZAP-70 positive CLL was associated with a shorter overall survival (median time 103 months vs. 293 months, p = 0.01) and a shorter time to disease progression (median time 26 months vs. 60 months, p = 0.01). In conclusion, ZAP-70 is expressed in several types of B-cell neoplasm and is easily detected by immunohistochemistry, providing a useful prognostic marker in patients with CLL from whom no other material is available or when other techniques for its assessment cannot be performed.
authors.affiliation: Haemopathology Unit, Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Carreras
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: Lluís
authors.initials: L
authors.lastname: Colomo
authors.forename: Carol
authors.initials: C
authors.lastname: Moreno
authors.forename: Santiago
authors.initials: S
authors.lastname: Ramón y Cajal
authors.forename: Marta
authors.initials: M
authors.lastname: Crespo
authors.forename: Frederic
authors.initials: F
authors.lastname: Tort
authors.forename: Francesc
authors.initials: F
authors.lastname: Bosch
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005803:Genes, Immunoglobulin / Q000235:genetics; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000737:chemistry* / Q000235:genetics; D020522:Lymphoma, Mantle-Cell / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D051746:ZAP-70 Protein-Tyrosine Kinase
chemical_list: D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human