title: ZAP-70 immunoreactivity is a prognostic marker of disease progression in chronic lymphocytic leukemia.
abstract: 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-70 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.
authors.affiliation: Ematologia I - Centro Trapianti di Midollo, IRCCS Ospedale Maggiore e Università degli Studi di Milano, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Vener
authors.forename: Umberto
authors.initials: U
authors.lastname: Gianelli
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.forename: Nicola Stefano
authors.initials: NS
authors.lastname: Fracchiolla
authors.forename: Franco
authors.initials: F
authors.lastname: Somalvico
authors.forename: Federica
authors.initials: F
authors.lastname: Savi
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Pasquini
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
authors.forename: Giorgio Lambertenghi
authors.initials: GL
authors.lastname: Deliliers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020732:Cytogenetic Analysis; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis / Q000378:metabolism*
chemical_list: D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human