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High ZAP-70 expression correlates with worse clinical outcome in mantle cell lymphoma

Leukemia volume 20, pages 1905–1908 (2006)Cite this article

Zeta-associated protein 70 (ZAP-70) is a ζ-chain, CD3-receptor-associated protein tyrosine kinase (PTK) that is critical for initiating T-cell signaling. Relatively little is known with regard to its function in B cells, although there is evidence that ZAP-70 may enhance signal transduction via the B-cell receptor complex. In chronic lymphocytic leukemia (CLL), the presence of >20% of ZAP-70-positive CLL cells detectable by flow cytometry was found to correlate with rapid disease progression and shorter overall survival in stage Binet A patients.1 High level of ZAP-70 expression also has been associated with a relative lack of somatic mutations in the variable regions of the immunoglobulin heavy chain gene (VH), which is an established prognostic marker for CLL.2 Several recent studies have confirmed that ZAP-70 is expressed in a subset of mantle cell lymphoma (MCL).3, 4, 5 In this study, we aimed to determine if ZAP-70 carries any clinical significance in newly diagnosed MCL patients.

Immunohistochemistry was employed to assess ZAP-70 expression in 64 MCL tumors. The clinical characteristics of these patients are summarized in Table 1. All cases were newly diagnosed and collected between 1994 and 2003 at the Department of Laboratory Medicine and Pathology, Cross Cancer Institute. Treatment for each MCL patient was determined during our weekly lymphoma conference based on our institutional treatment protocol. For first-line treatment, 32 of the 64 patients received CHOP-based (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, 15 had chlorambucil-based chemotherapy, and five received other treatments such as proteasome inhibitor PS341 and flavopirodol. The diagnosis of all MCL cases was based on the criteria described in the World Health Organization Classification Scheme; all cases were positive for CD5 and/or CD43 and cyclin D1, and negative for CD23. All tissues were routinely processed, formalin-fixed and paraffin-embedded. All but four cases had the small cell morphology. Three of the remaining four cases were blastoid MCL. The morphology of the other case was composed of diffuse areas of small lymphoma cells admixed with nodules of large blastoid cells. None of the cases demonstrated a predominantly (i.e., >85%) mantle zone pattern.

Table 1 Summary of clinical data in ZAP-70high and ZAP-70low MCL patients
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Acknowledgements

Research grant support was received from the National Cancer Institute of Canada and Canadian Cancer Society.

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Authors and Affiliations

  1. Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

    D Hui

  2. Department of Laboratory Medicine and Pathology, Cross Cancer Institute, Edmonton, Alberta, Canada

    L Dabbagh & R Lai

  3. Department of Epidemiology, Cross Cancer Institute, Edmonton, Alberta, Canada

    J Hanson

  4. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    H M Amin

  5. Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada

    R Lai

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  1. D Hui
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Correspondence to R Lai.

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Hui, D., Dabbagh, L., Hanson, J. et al. High ZAP-70 expression correlates with worse clinical outcome in mantle cell lymphoma. Leukemia 20, 1905–1908 (2006). https://doi.org/10.1038/sj.leu.2404362

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