In B-CLL serum thymidine kinase (s-TK) levels, that are probably related to the proliferative activity of the disease, and ZAP-70 expression on leukemic cells were both recent-ly proposed as relevant biological prognostic factors, asso-ciated to the mutational IgVH gene status. In order to com-pare the prognostic significance of s-TK and of ZAP-70, we evaluated 83 patients affected by B-CLL in whom both s-TK levels and ZAP-70 expression at presentation were available. They were 53 males (64%), aged 34 to 83 years (median60). At diagnosis 57(69%)were Binet stageA, 20 (24%) stage B and 6 (7%) stage C. The median follow-up period from diagnosis was 51 months (range 7–197 months).The levels of TK activity in the sera, obtained at diagnosis and stored at –20°C until analysis, were mea- sured by a commercially available radioenzyme assay (Immmunotech; Beckman Coulter), and expressed in units per liter. Control values of s-TK, as determined in 24 healthy adults, were 3.1 + 2.2 U/L (mean + SD; range 0.3- .7.2 U/L). The cytoplasmic expression of ZAP-70 protein in leukemic cells was evaluated by immunohistochemical methods on bone marrow trephine biopsies taken within 6 months from presentation, using a mouse anti-human monoclonal antibody to ZAP-70 (clone 2F3.2, 1/200, Upstate, Lake Placid NY). s-TK levels were elevated (i.e.>= 8 U/L) in 39 patients (47%). In 44 cases (53%) cytoplasmic expression of ZAP-70 was present; 27 of them (60.4%) had elevated s-TK levels. Conversely, in 27/39 ZAP-70 negative cases (69%) s-TK was normal. Overall, in 54/83 cases (65%) s-TK and ZAP-70 data were concordant. Mean s- TK levels of ZAP-70 positive and ZAP-70 negative patients were 14.8 U/l (+/- 6.8 SD) and 7.6 U/L (+/- 7.1 SD) respec- tively (p<0.01). At univariate analysis both elevated s-TK levels and ZAP-70 expression were associated with inferi- or progression free survival (PFS) (p=0.0007 and p=0.005 respectively). Combining the 2 parameters we found that PFS at 5 years was significantly better (61% +/- 9%) in ZAP-70 negative patients with normal s-TK as compared to patients with either positive expression of ZAP-70 or elevated s-TK levels (28%+/- 9%; p=0.01), or both ZAP-70 positivity and elevated s-TK levels (17%+7%; p=0.0006). In conclusion, our findigs suggest that the combined assessment of s-TK levels and ZAP-70 expression can improve the prognostic evaluation of B-CLL at diagnosis.
PROGNOSTIC VALUE OF SERUM THYMIDINE KINASE LEVEL AND ZAP-70 EXPRESSION DETECTED BY IMMUNOHISTOCHEMISTRY ON BONE MARROW BIOPSIES IN B-CLL: COMPARATIVE ANALYSIS
ZANOTTI, ROBERTA;AMBROSETTI, Achille;SCUPOLI, Maria;Lestani, Maurizio;PIZZOLO, Giovanni
2005-01-01
Abstract
In B-CLL serum thymidine kinase (s-TK) levels, that are probably related to the proliferative activity of the disease, and ZAP-70 expression on leukemic cells were both recent-ly proposed as relevant biological prognostic factors, asso-ciated to the mutational IgVH gene status. In order to com-pare the prognostic significance of s-TK and of ZAP-70, we evaluated 83 patients affected by B-CLL in whom both s-TK levels and ZAP-70 expression at presentation were available. They were 53 males (64%), aged 34 to 83 years (median60). At diagnosis 57(69%)were Binet stageA, 20 (24%) stage B and 6 (7%) stage C. The median follow-up period from diagnosis was 51 months (range 7–197 months).The levels of TK activity in the sera, obtained at diagnosis and stored at –20°C until analysis, were mea- sured by a commercially available radioenzyme assay (Immmunotech; Beckman Coulter), and expressed in units per liter. Control values of s-TK, as determined in 24 healthy adults, were 3.1 + 2.2 U/L (mean + SD; range 0.3- .7.2 U/L). The cytoplasmic expression of ZAP-70 protein in leukemic cells was evaluated by immunohistochemical methods on bone marrow trephine biopsies taken within 6 months from presentation, using a mouse anti-human monoclonal antibody to ZAP-70 (clone 2F3.2, 1/200, Upstate, Lake Placid NY). s-TK levels were elevated (i.e.>= 8 U/L) in 39 patients (47%). In 44 cases (53%) cytoplasmic expression of ZAP-70 was present; 27 of them (60.4%) had elevated s-TK levels. Conversely, in 27/39 ZAP-70 negative cases (69%) s-TK was normal. Overall, in 54/83 cases (65%) s-TK and ZAP-70 data were concordant. Mean s- TK levels of ZAP-70 positive and ZAP-70 negative patients were 14.8 U/l (+/- 6.8 SD) and 7.6 U/L (+/- 7.1 SD) respec- tively (p<0.01). At univariate analysis both elevated s-TK levels and ZAP-70 expression were associated with inferi- or progression free survival (PFS) (p=0.0007 and p=0.005 respectively). Combining the 2 parameters we found that PFS at 5 years was significantly better (61% +/- 9%) in ZAP-70 negative patients with normal s-TK as compared to patients with either positive expression of ZAP-70 or elevated s-TK levels (28%+/- 9%; p=0.01), or both ZAP-70 positivity and elevated s-TK levels (17%+7%; p=0.0006). In conclusion, our findigs suggest that the combined assessment of s-TK levels and ZAP-70 expression can improve the prognostic evaluation of B-CLL at diagnosis.
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