ZAP-70 Found in CLL, Other Blood Cancers

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J Pathol. 2005 Feb 1; [Epub ahead of print]

Immunohistochemical analysis of ZAP-70 expression in B-cell lymphoid

neoplasms.

Carreras J, Villamor N, Colomo L, Moreno C, Cajal SR, Crespo M, Tort

F, Bosch F, -Guillermo A, Colomer D, Montserrat E, Campo E.

Haemopathology Unit, Departments of Pathology and Haematology,

Hospital Clinic, Institut d'Investigacions Biomediques August Pi i

Sunyer, Barcelona, Spain.

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.

Copyright © 2005 Pathological Society of Great Britain and Ireland.

Published by Wiley & Sons, Ltd.

PMID: 15685592 [PubMed - as supplied by publisher]