Genetic Abnormalities in Biliary Brush Samples for Distinguishing Cholangiocarcinoma from Benign Strictures in Primary Sclerosing Cholangitis
Table 2
Diagnostic performance of cytology, FISH, and measures of clonal diversity in distinguishing benign from malignant strictures.
PSC
CCA
value
Sensitivity
Specificity
AUC (95% CI)
Cytology
Cytology (M), (%)
0 (0)
3 (25)
0.021
25%
100%
0.63 (0.43–0.83)
Cytology (S + M), (%)
1 (3)
6 (50)
0.001
50%
97%
0.73 (0.54–0.93)
FISH markers
CDKN2A loss, (%)
9 (31)
8 (67)
0.045
67%
69%
0.68 (0.49–0.86)
TP53 loss, (%)
1 (3)
2 (17)
0.20
17%
97%
0.57 (0.36–0.77)
ERBB2 gain, (%)
2 (7)
0 (0)
1.00
0%
93%
0.47 (0.28–0.66)
20q gain, (%)
12 (41)
8 (67)
0.181
67%
59%
0.63 (0.44–0.82)
MYC gain, (%)
6 (21)
7 (58)
0.029
58%
79%
0.69 (0.50–0.88)
CEP7 gain, (%)
7 (24)
7 (58)
0.068
58%
76%
0.67 (0.48–0.86)
CEP17 gain, (%)
16 (55)
10 (83)
0.154
83%
45%
0.64 (0.46–0.82)
Cytology and FISH
Cytology (S + M) and CDKN2A, (%)
10 (34)
10 (83)
0.006
83%
66%
0.74 (0.58–0.91)
Cytology (S + M) and MYC, (%)
7 (24)
10 (83)
0.001
83%
76%
0.80 (0.64–0.95)
Cytology (S + M) and MYC/CDKN2A, (%)
14 (48)
11 (92)
0.013
92%
52%
0.72 (0.56–0.88)
Diversity measures
Richness (set 1)
11
10
0.015
83%
62%
0.73 (0.56–0.89)
Richness (set 2)
8
10
0.002
83%
72%
0.78 (0.62–0.94)
Shannon diversity (set 1)
8
10
0.002
83%
72%
0.78 (0.62–0.94)
Shannon diversity (set 2)
10
10
0.006
83%
65%
0.74 (0.58–0.91)
Diversity measures and cytology
Cytology and richness (set 2)
9
11
<0.001
92%
69%
0.80 (0.66–0.95)
Cytology and Shannon diversity (set 1)
9
11
<0.001
92%
69%
0.80 (0.66–0.95)
values are compared using Fisher’s exact test. M refers to malignant and S refers to suspicious. CCA includes 3 patients with PSC-associated CCA and 9 patients with sporadic CCA. AUC: area under the curve; CCA: cholangiocarcinoma; CI: confidence interval; PSC: primary sclerosing cholangitis; NA: not applicable. Cut-off values for measures of clonal diversity were determined using ROC curves and were 4.5 for richness (set 1), 5.5 for richness (set 2), 0.34 for Shannon diversity (set 1), and 0.43 for Shannon diversity (set 2).
