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28
100
Overall
51 (51.0)
Male
63
23-88
55(55.0)
45(45.0)
Median
Range
<65
.≥65
1-147
Range
43 (43.0)
NET G2
Tumor Location
57 (57.0)
NET G1
WHO classification (2010)
43.5
Median
Follow-up, months
Outcome
60.8 (SD, 15.1)
Mean
Age, years
49 (49.0)
Female
Gender
No. of Patients (%)
Variable
92.1
95.7
94.5
93.8
91.4
97.1
94.1
3 years
Table 1. Clinicopathological Parameters and Outcome (n=100)
82.4
95.7
94.5
85.6
80.8
97.1
89.2
5 years
0.5429
0.0974
0.749
0.1245
(P Value)
Log-rank
Overall Survival (%)
74.1
97.6
86.9
87.7
82.3
93.0
87.2
3years
70.0
97.6
82.6
87.7
82.4
89.1
85.2
5 years
Recurrence-Free Survival (%)
0.1632
0.0005
0.708
0.4577
(P Value)
Log-rank
44 (44.0)
Body/tail
20
0.8-156
51 (52.6)
46 (47.4)
Median
Range
≤20 mm
.>20 mm
23 (23.0)
Positive
8 (8.0)
Positive
25(25.0)
Functioning
Negative
55(60.4)
20(22.0)
Positive
Vascular invasion
71(78.0)
Negative
Lymphatic invasion
75(75.0)
Non-functioning
Type of hormone production
92 (92.0)
Negative
Liver metastasis
77 (77.0)
Negative
Nodal metastasis
24.3 (SD, 20.8)
Mean
Tumor size, mm
56 (56.0)
Head
97.7
94.7
94.8
100
92.1
57.1
97.5
84.4
96.9
94.9
97.6
95.7
92.1
97.7
81.2
91.5
100
84.2
42.9
94.9
72.4
94.1
86.4
97.6
91.8
85.5
0.0142
0.1963
0.2424
<.0001
0.0513
0.1293
97.6
84.4
86.3
90.7
85.9
50.0
88.7
87.2
89.5
72.6
100
92.9
79.5
94.1
84.4
83.7
90.7
82.3
50.0
86.5
74.7
87.1
68.1
100
89.6
79.5
0.0003
0.2342
0.2010
0.0080
0.1286
<0.0001
22(24.7)
positive
58(58.6)
Positive (intact)
35(35.4)
Positive (intact)
74(74.7)
Positive (intact)
41(41.4)
Positive (intact)
abnormal (loss)
65(67.0)
61(62.2)
Positive (intact)
p53
37(37.8)
Negative (loss)
PTEN
58(58.6)
Negative (loss)
TSC2 (tuberin)
25(25.3)
Negative (loss)
MEN1 (Menin)
64(64.6)
Negative (loss)
DAXX
41(41.4)
Negative (loss)
ATRX
Immunohistochemistry
67(75.3)
36(39.6)
Negative
Perineural infiltration
Positive
92.9
98.3
90.1
100
89.1
95.3
90.4
93.7
94.5
97.9
88.6
84.0
98.2
90.3
89.0
94.0
84.1
100
79.7
91.2
84.0
93.7
88.1
93.0
84.0
44.8
98.2
77.3
0.1975
0.0486
0.007
0.5940
0.7908
0.0558
0.0002
87.0
88.6
84.5
94.2
79.3
88.4
83.7
95.7
83.0
92.8
78.9
60.7
91.8
67.1
83.8
88.6
78.4
94.2
74.9
85.5
83.7
95.7
80.1
92.8
74.3
60.7
89.0
67.1
0.4697
0.0721
0.009
0.3759
0.2882
0.0117
0.00124
54(54.6)
Positive (intact)
29(29.3)
70(70.7)
Negative (loss)
Positive (intact)
P16
45(45.4)
32(33.0)
Negative (loss)
Rb1
normal (intact)
95.0
96.0
95.9
92.1
100
91.6
87.3
85.2
92.1
93.4
0.3067
0.4927
88.5
85.1
85.6
88.2
85.2
85.6
85.1
85.6
84.2
85.2
0.7769
0.5786
Table 2. Multivariate Analysis of Relapse-Free Survival for patients with G2 PNETS including Loss of
Combined Gene Protein Expression
Variables
Hazard Ratio
95% CI
TSC2 and ATRX negative
10.1
2.1-66.9
0.003
Vascular invasion
10.9
1.3-10.3
0.02
Nodal metastasis
5.8
1.2-29.3
0.02
Perineural invasion
2.1
0.5-10.3
0.46
Table 3. Summary of significant association between phenotypes and clinicopathological parameters (n=100)
ATRX negative (loss)
MEN1 negative (loss)
TSC2 negative (loss)
PTEN negative (loss)
Clinicopathological Parameters
35
Perineural invasion
0.002
Venous invasion
0.004
Nodal metastasis
0.014
Tumor size (>20 mm)
0.021
Recurrence
0.041
Hormone production
0.003
Venous invasion
0.012
Grade
0.02
Liver metastasis
0.023
Tumor size (>20 mm)
0.029
Hormone production
0.0008
Nodal metastasis
0.001
Recurrence
0.01
Liver metastasis
0.019
Tumor size (>20 mm)
0.024
Venous invasion
0.03
Venous invasion
0.007
Tumor size (>20 mm)
0.02
Recurrence
0.044
25
58
32
P value
0.2
0.4
0.6
0.8
1.0
Overall Survival (probability)
12
24
36
60
72
84
OS months
48
Log-rank 0.055
96 108 120
ATRX (‐), n=41
ATRX (+), n=58
ATRX positive (intact)
0.2
0.4
0.6
0.8
1.0
Figure 1
Relapse‐Free Survival (probability)
12
24
36
48
Log-rank 0.011
72
84
RFS months
60
96
ATRX (‐), n=41
108 120
ATRX (+), n=58
ATRX negative (loss)
Overall Survival (probability)
0.2
0.4
0.6
0.8
1.0
12
24
36
Log‐rank 0.007
60
72
OS months
48
84
96
TSC2 (‐), n=58
TSC2 (+), n=41
108 120
TSC2 positive (intact)
0.2
0.4
0.6
0.8
1.0
Figure 2
Relapse‐Free Survival (probability)
12
24
36
48
Log‐rank 0.009
72
84
RFS months
60
96
TSC2 (‐), n=58
TSC2 (+), n=41
108 120
TSC2 negative (loss)
0.2
0.4
0.6
0.8
1.0
Overall Survival (probability)
12
24
36
Log‐rank 0.04
60
72
OS months
48
84
PTEN (‐), n=37
PTEN (+), n=61
96 108 120
PTEN positive (intact)
0.2
0.4
0.6
0.8
1.0
Figure 3
Relapse‐Free Survival (probability)
12
24
36
Log‐rank 0.07
48
72
84
RFS months
60
96 108 120
PTEN (‐), n=37
PTEN (+), n=61
PTEN negative (loss)
0.2
0.4
0.6
0.8
1.0
Overall Survival (probability)
12
24
36
48
TSC2 (+) and ATRX (+)
TSC2 or ATRX (‐)
TSC2 (‐) and ATRX (‐)
72
84
108
P=0.008
96
Log‐rank test
P=0.11
P=0.14
OS months
60
TSC2 (‐) and ATRX (‐), n=31
TSC2 or ATRX (‐), n=37
TSC2 (+) and ATRX (+), n=31
120
0.2
0.4
0.6
0.8
1.0
Figure 4 Relapse-Free Survival (probability)
24
36
48
TSC2 (+) and ATRX (+)
TSC2 or ATRX (‐)
TSC2 (‐) and ATRX (‐)
12
72
84
108
P=0.003
96
Log‐rank test
P=0.005
P=0.73
RFS months
60
TSC2 (‐) and ATRX (‐), n=31
TSC2 (+) and ATRX (+), n=31
TSC2 or ATRX (‐), n=37
120
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