title: Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma.
abstract: Using immunohistochemical methods, we evaluated zeta-associated protein (ZAP)-70 expression in 341 cases of non-Hodgkin and Hodgkin lymphoma. In B-cell NHL, ZAP-70 was positive in five of six (83%) precursor B-lymphoblastic lymphoma, 11 of 37 (30%) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), five of 39 (13%) mantle cell lymphoma, one of 12 (8%) Burkitt lymphoma, and one of 12 (8%) nodal marginal zone B-cell lymphoma. In 22 cases of CLL/SLL, seven of nine (78%) with unmutated IgVH genes expressed ZAP-70, compared with one of 13 (8%) with mutated IgVH genes (P=0.0015 Fisher's exact test). ZAP-70 expression was not detected in diffuse large B-cell lymphoma (n=26), extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (n=24), follicular lymphoma (n=21), plasma cell myeloma/plasmacytoma (n=10), lymphoplasmacytic lymphoma (n=10), or splenic marginal zone lymphoma (n=6). In T/NK-cell NHL, ZAP-70 was positive in all extranodal natural killer (NK) / T-cell lymphoma, nasal-type (n=6) and enteropathy-type T-cell lymphoma (n=4), four of five (80%) subcutaneous panniculitis-like T-cell lymphoma, six of eight (75%) mycosis fungoides, three of five (60%) precursor T-lymphoblastic lymphoma, 10 of 17 (59%) peripheral T-cell lymphoma, two of four (50%) blastic NK-cell lymphoma, one of three (33%) T-cell prolymphocytic leukemia, 13 of 52 (25%) anaplastic large cell lymphoma, and one of six (17%) angioimmunoblastic T-cell lymphoma. Seven of 12 (58%) cutaneous CD30-positive lymphoproliferative disorders were also ZAP-70-positive. In Hodgkin lymphoma, ZAP-70 was negative in neoplastic cells in all cases tested. ZAP-70 staining in B-cell lymphomas and reactive T cells was predominantly nuclear with variable cytoplasmic staining. By contrast, ZAP-70 staining in T/NK-cell lymphomas was heterogeneous, and a shift from predominantly nuclear to predominantly cytoplasmic staining was observed, particularly in those neoplasms with high-grade morphology. In summary, ZAP-70 is expressed by many lymphoma types, correlates with immunoglobulin heavy-chain variable region gene mutational status in CLL/SLL, and can be detected reliably using immunohistochemical methods.
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Joan H
authors.initials: JH
authors.lastname: Admirand
authors.forename: George Z
authors.initials: GZ
authors.lastname: Rassidakis
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: Jose R
authors.initials: JR
authors.lastname: Valbuena
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D005260:Female; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007150:Immunohistochemistry; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D051746:ZAP-70 Protein-Tyrosine Kinase
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human