The reaction mixture then was aspirated into the measuring cell, where the microparticles were captured magnetically upon the surface of the electrode. Unbound reactants were removed with a phosphate-tripropylamine buffer. Application of voltage to the electrode then inhibitor JQ1 induced chemiluminescent emission that was measured by a photomultiplier. For comparison, conventional tumour markers (CEA, CA 19-9, and AFP) were measured by a chemiluminescent immunoassay (CLIA). Statistical analysis Data are given as the median with 25th and 75th percentiles of marker concentrations. Kruskal�CWallis one-way analysis of variance was performed initially for multiple-comparison tests. When this analysis was significant, pairs of groups were compared using the Mann�CWhitney U-test.
To compare abilities of tumour markers to distinguish patients with primary liver cancers from those with benign liver disease, receiver operator characteristic (ROC) curves, which correlate true- and false-positive rates (sensitivity and (1?specificity)), were constructed using the ROCKIT program (Metz et al, 1998a, 1998b). In addition, areas under the ROC curve (AUC) were calculated for each marker. The statistical significance of differences between the two AUCs also was determined. RESULTS CYFRA 21-1 distribution and histologic type of primary liver cancer Significant differences in CYFRA 21-1 concentration (median and interquartile range) were noted between patients with primary liver cancer (1.9; interquartile range 1.1�C3.1ngml?1) and those with benign liver disease (1.4; 1.0�C1.9; Mann�CWhitney U-test, P=0.
0009). Distributions of serum CYFRA 21-1 concentrations for HCC (1.7; 1.1�C2.7), ICC (5.0; 3.1�C10.7), and benign liver disease are shown in Figure 1. Significantly higher concentrations of CYFRA 21-1 were noted in patients with ICC than in those with benign liver disease (Mann�CWhitney U-test, P<0.0001) or HCC (P<0.0001). Figure 1 Distribution of individual serum CYFRA 21-1 concentrations in patients with primary liver cancer and benign liver diseases. Data are presented as upper and lower quartile and range (box), median value (horizontal line), and middle 90% distribution ... Sensitivities of CYFRA 21-1 and other tumour markers Table 2 shows the results for serum concentration and sensitivity of AFP, CEA, CA 19-9, and CYFRA 21-1 in relation to histological type.
When cutoff values were selected according to 95% specificity in the benign group, the cutoff values were 20.3ngml?1 for AFP, 4.8ngml?1 for CEA, 47.0Uml?1 for CA 19-9, and 3.0ngml?1 for CYFRA 21-1. Cilengitide AFP demonstrated a higher sensitivity (59.1%) than other markers in patients with HCC. In patients with ICC, the most sensitive marker was CYFRA 21-1 (87.0%). Although CA 19-9 showed relatively high sensitivity in ICC patients (60.