[Show abstract][Hide abstract] ABSTRACT: Zeta-chain associated protein (ZAP)-70 has been proposed as a surrogate marker for immunoglobulin heavy-chain variable region (IgVH) mutation in chronic lymphocytic leukemia (CLL), but it is still not clear whether it is an independent prognostic factor.
The authors evaluated ZAP-70 expression by flow cytometry in 201 untreated patients and correlated ZAP-70 levels with CD38 expression, genetic abnormalities detected by fluorescence in situ hybridization (FISH), and the time from diagnosis to first treatment.
Fifty-seven patients (28%) were positive for ZAP-70 (> or = 20%). Positive ZAP-70 status was associated with advanced disease stage, atypical morphology, CD38-positive status, trisomy 12, del(6q), or no detectable abnormalities; negative ZAP-70 status was correlated with del(13q) as a sole abnormality. The treatment-free interval (TFI) was 17.7 months for ZAP-70-positive patients and 44.6 months for ZAP-70-negative patients (P < 0.001). Multivariate analysis in 117 patients identified advanced stage, CD38 > or = 7%, and the absence of del(13q) as a sole abnormality as independent factors for short TFI. Excluding FISH, ZAP-70 status acquired independent prognostic value along with CD38 status. The authors proposed a risk model that combines ZAP-70 and CD38 to identify patients who are likely to progress. When both markers were positive, the TFI was 12 months; when both were negative, the median TFI was 54 months; a median TFI of 26 months was observed in patients who had discordant results (P < 0.00001).
The current findings suggested that both ZAP-70 and CD38 should be tested prospectively in all patients with early-stage CLL.
Cancer 11/2005; 104(10):2124-32. · 4.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe a progressive mantle cell lymphoma (MCL) in which multicolor fluorescence in situ hybridization (M-FISH) on metaphases did not detect the characteristic t(11;14)(q13;q32), although translocations of chromosomes 11 with 15, and 14 with 15 were observed. When CCND1/IGH probes were hybridized to metaphases, however, cryptic fusion signals were detected on the der(11) and der(14) sites of CCND1 (11q13) and IGH (14q32), revealing a complex translocation involving chromosomes 11, 14, and 15. Interphase FISH with CCND1/IGH probes revealed varying patterns with one or two fusion signals, and some with no clear evidence of fusion. Loss of 17p and gain of 3q, known to be associated with disease progression in MCL, were detected with M-FISH and confirmed with the use of p53 and BCL6 probes together with comparative genomic hybridization, which detected also an interstitial deletion on 7p21. This case further illustrates the value of M-FISH in combination with fusion probes in elucidating complex cytogenetic abnormalities.
Cancer Genetics and Cytogenetics 11/2004; 154(1):67-71. · 1.93 Impact Factor