ZAP-70 immunoreactivity is a prognostic marker of disease progression in chronic lymphocytic leukemia

The expression of zeta-associated protein 70 (ZAP-70) in chronic lymphocytic leukemia (CLL) seems to correlate with the mutational status of the immunoglobulin heavy-chain variable-region genes, clinical course and patient prognosis. The aim was to determine the prognostic significance of the immunohistochemical expression of ZAP-70 protein in CLL by means of the long-term follow-up of 108 patients. This study identified 3 patterns of ZAP-70 immunoreactivity: negative (58 patients, 54%), weakly positive (20 patients, 18%) and strongly positive (30 patients, 28%). Overall, ZAP-70 immunoreactivity correlated with an abnormal karyotype (p = 0.017), a lymphocyte doubling time (LDT) of <6 months (p = 0.001) and <12 months (p = 0.01), Rai II - IV and Binet B-C stage (p = 0.013), the clinical need for chemotherapy (p <0.001) and the need for more than 1 chemotherapy line (p <0.001). Kaplan-Meier analysis demonstrated that ZAP-70 immunoreactivity closely correlated with a shorter LDT (p <0.0001) and time from diagnosis to initial therapy (p = 0.0001). The same significance was retained when the patients were stratified into the ZAP-70 immunoreactivity groups (p <0.0001). This study shows that ZAP- immunoreactivity can be a reliable prognostic marker in CLL and proposes a system for evaluating the results. The observations support the inclusion of the immunohistochemical expression of ZAP-70 in clinical trials involving CLL patients.