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: Joan H Admirand, George Z Rassidakis, Lynne V Abruzzo, Jose R Valbuena, Dan Jones, L Jeffrey Medeiros
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 17 Issue 8 Pg. 954-61 (Aug 2004) ISSN: 0893-3952 [Print] United States
• PMID: 15133473 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Immunoglobulin Heavy Chains
• Immunoglobulin Variable Region
• Protein-Tyrosine Kinases
• ZAP-70 Protein-Tyrosine Kinase
• ZAP70 protein, human

Topics

• Blotting, Western
• Cell Line, Tumor
• DNA Mutational Analysis
• Female
• Hodgkin Disease (genetics, metabolism, pathology)
• Humans
• Immunoglobulin Heavy Chains (genetics)
• Immunoglobulin Variable Region (genetics)
• Immunohistochemistry
• Jurkat Cells
• Killer Cells, Natural (metabolism, pathology)
• Lymphoma, B-Cell (genetics, metabolism, pathology)
• Lymphoma, Non-Hodgkin (genetics, metabolism, pathology)
• Lymphoma, T-Cell (genetics, metabolism, pathology)
• Male
• Protein-Tyrosine Kinases (analysis)
• ZAP-70 Protein-Tyrosine Kinase