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

• Published in: The Journal of pathology Vol. 205; no. 4; pp. 507 - 513
• Main Authors: Carreras, Joaquim, Villamor, Neus, Colomo, Lluís, Moreno, Carol, Cajal, Santiago Ramón y, Crespo, Marta, Tort, Frederic, Bosch, Francesc, López-Guillermo, Armando, Colomer, Dolors, Montserrat, Emili, Campo, Elías
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2005; Wiley
• Subjects: Adult; Aged; Aged, 80 and over; B-cell lymphoproliferative disorders; Biological and medical sciences; Female; Flow Cytometry - methods; Genes, Immunoglobulin - genetics; Hematologic and hematopoietic diseases; Hodgkin Disease - genetics; Hodgkin Disease - metabolism; Humans; immunohistochemistry; Immunohistochemistry - methods; Investigative techniques, diagnostic techniques (general aspects); Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell - chemistry; Lymphoma, B-Cell - genetics; Lymphoma, Mantle-Cell - genetics; Lymphoma, Mantle-Cell - metabolism; Male; Medical sciences; Middle Aged; Mutation; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Prognosis; Protein-Tyrosine Kinases - analysis; ZAP-70; ZAP-70 Protein-Tyrosine Kinase; Immunohistochemistry; ZAP-70; Anatomic pathology; Lymphoid cell; Lymphoproliferative syndrome; Malignant hemopathy; B-Lymphocyte; β Cell; B-cell lymphoproliferative disorders
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.1727

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 IgVH 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). IgVH 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 IgVH gene in an unmutated configuration, whereas all but one ZAP‐70‐negative CLL had somatically hypermutated IgVH. The 12 MCLs analysed were ZAP‐70 negative regardless of IgVH 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 John Wiley & Sons, Ltd.