01.12.2017 | Research article | Ausgabe 1/2017 Open Access

Prognostic and predictive factors in patients with metastatic or recurrent cervical cancer treated with platinum-based chemotherapy.
- Zeitschrift:
- BMC Cancer > Ausgabe 1/2017
Background
Methods
Patient selection
Immunohistochemistry
Staining evaluation
Genotyping
Statistical analysis
Results
Demographics
Characteristic
|
No of patients (%)
|
p-value
|
|
---|---|---|---|
ITP
|
IP
|
||
Total patients
|
22
|
21
|
|
Age (years)
|
|||
Median
|
58
|
58
|
0.646
|
Range
|
32–78
|
35–75
|
|
Histology
|
|||
Squamous
|
13 (59.1)
|
18 (85.7)
|
0.129
|
Adenocarcinoma
|
4 (18.2)
|
2 (9.5)
|
|
Mixed
|
5 (22.7)
|
1 (4.8)
|
|
Overall response
|
|||
CR
|
5 (22.7)
|
1 (4.8)
|
0.038
|
PR
|
10 (45.5)
|
4 (19)
|
|
SD
|
2 (9.1)
|
5 (23.8)
|
|
PD
|
5 (22.7)
|
11 (52.4)
|
Protein Expression
|
No of patients (%)
|
p-value
|
|
---|---|---|---|
ITP
|
IP
|
||
ERCC 1
|
|||
High
|
11 (50)
|
9 (42.9)
|
0.906
|
Moderate
|
5 (22.7)
|
7 (33.3)
|
|
Low
|
2 (9.1)
|
2 (9.5)
|
|
None
|
4 (18.2)
|
3 (14.3)
|
|
COX 2
|
|||
High
|
7 (31.8)
|
5 (23.8)
|
0.342
|
Moderate
|
5 (22.7)
|
7 (33.3)
|
|
Low
|
4 (18.2)
|
7 (33.3)
|
|
None
|
6 (27.3)
|
2 (9.5)
|
|
III beta tubulin
|
|||
High
|
11 (50)
|
9 (42.9)
|
0.425
|
Moderate
|
8 (36.4)
|
5 (23.8)
|
|
Low
|
3 (13.6)
|
6 (28.6)
|
|
None
|
0 (0)
|
1 (4.8)
|
|
CD4
|
|||
High
|
0 (0)
|
0 (0)
|
0.768
|
Moderate
|
3 (13.6)
|
4 (19)
|
|
Low
|
6 (27.3)
|
7 (33.3)
|
|
None
|
13 (59.1)
|
10 (47.6)
|
|
CD8
|
|||
High
|
1(4.5)
|
0 (0)
|
0.226
|
Moderate
|
3 (13.6)
|
3 (14.3)
|
|
Low
|
3 (13.6)
|
8 (38.1)
|
|
None
|
15 (68.2)
|
10 (47.6)
|
SNPs
|
No of patients (%)
|
p-value
|
|
---|---|---|---|
ITP
|
IP
|
||
MDR1 C3435T
|
|||
Polymorphisms
|
|||
CT
|
13 (59.1)
|
14 (66.6)
|
1
|
CC
|
4 (18.2)
|
3 (14.3)
|
|
TT
|
5 (22.7)
|
4 (19)
|
|
MDR1 G2677 T
|
|||
Polymorphisms
|
|||
GT
|
5 (22.7)
|
5 (23.8)
|
0.904
|
GG
|
15 (68.2)
|
13 (61.9)
|
|
TT
|
2 (9.1)
|
3 (14.3)
|
|
ERCC1 C8092A
|
|||
Polymorphisms
|
|||
CA
|
9 (40.9)
|
8 (38.1)
|
1
|
CC
|
11 (50)
|
10 (47.6)
|
|
AA
|
2 (9.1))
|
3 (14.3)
|
|
ERCC1 N118 N
|
|||
Polymorphisms
|
|||
CT
|
8 (36.4)
|
12 (57.1)
|
0.371
|
CC
|
3 (13.6)
|
3(14.3)
|
|
TT
|
11 (50)
|
6 (28.6)
|
Protein expression association with patient characteristics
Genotype distributions and their association with patient characteristics and protein expression
Immunohistochemisrty associations with response and survival outcomes
Median OS (months)
|
Median PFS (months)
|
|||||||
---|---|---|---|---|---|---|---|---|
Protein Expression
|
Low
|
High
|
P-value
|
Low
|
High
|
P-value
|
||
ERCC1
|
21.4
|
10.5
|
0.006
|
10.2
|
5.1
|
0.027
|
||
COX2
|
17.7
|
10.5
|
0.051
|
6.5
|
5.2
|
0.463
|
||
Tubulin B3
|
11.6
|
11.9
|
0.704
|
6
|
6
|
0.347
|
||
CD4
|
11.9
|
11.9
|
0.446
|
5.6
|
8.8
|
0.253
|
||
CD8
|
13.5
|
8.6
|
0.041
|
6
|
3.9
|
0.766
|
||
SNPs
|
||||||||
MDR1 C3435T
|
CC
|
TT
|
CT
|
P-value
|
CC
|
TT
|
CT
|
P-value
|
20.2
|
16.5
|
10.5
|
0.19
|
7.9
|
6.6
|
6
|
0.654
|
|
MDR1 G2677 T
|
GG
|
TT
|
GT
|
GG
|
TT
|
GT
|
||
8.6
|
3.6
|
17.7
|
0.119
|
5.1
|
2.9
|
8.6
|
0.027
|
|
ERCC1C8092A
|
AA
|
CC
|
CA
|
AA
|
CC
|
CA
|
||
25.2
|
11.6
|
15.4
|
0.756
|
2.8
|
6
|
6
|
0.543
|
|
ERCC1 N118 N
|
CC
|
TT
|
CT
|
CC
|
TT
|
CT
|
||
8.2
|
21.4
|
8.5
|
0.063
|
5.2
|
8.8
|
3.9
|
0.006
|
Median OS (months)
|
Median PFS (months)
|
|||||||
---|---|---|---|---|---|---|---|---|
Protein Expression
|
Low
|
High
|
P-value
|
Low
|
High
|
P-value
|
||
ERCC1
|
21.4
|
10.5
|
0.049
|
8.2
|
6
|
0.558
|
||
COX2
|
17.7
|
10.5
|
0.363
|
7.9
|
6
|
0.895
|
||
Tubulin B3
|
11.9
|
16.4
|
0.529
|
8.2
|
7.9
|
0.74
|
||
CD4
|
11.9
|
25.5
|
0.397
|
6.6
|
10.1
|
0.113
|
||
CD8
|
11.9
|
5.4
|
0.476
|
7.9
|
1.2
|
0.707
|
||
SNPs
|
||||||||
MDR1 C3435T
|
CC
|
TT
|
CT
|
P-value
|
CC
|
TT
|
CT
|
P-value
|
3.4
|
11.9
|
11.7
|
0.467
|
1.8
|
8.8
|
8.1
|
0.484
|
|
MDR1 G2677 T
|
GG
|
TT
|
GT
|
GG
|
TT
|
GT
|
||
11.9
|
2.9
|
21.9
|
0.647
|
6.5
|
2.9
|
8.6
|
0.494
|
|
ERCC1C8092A
|
AA
|
CC
|
CA
|
AA
|
CC
|
CA
|
||
25.2
|
11.9
|
11.9
|
0.664
|
10.2
|
7.9
|
6.5
|
0.702
|
|
ERCC1 N118 N
|
CC
|
TT
|
CT
|
CC
|
TT
|
CT
|
||
11.6
|
21.6
|
5.6
|
0.401
|
8.2
|
10.1
|
3.6
|
0.003
|
Median OS (months)
|
Median PFS (months)
|
|||||||
---|---|---|---|---|---|---|---|---|
Protein Expression
|
Low
|
High
|
P-value
|
Low
|
High
|
P-value
|
||
ERCC1
|
20.2
|
8.6
|
0.114
|
20.2
|
3.9
|
0.045
|
||
COX2
|
15.4
|
8.6
|
0.106
|
5.1
|
2.9
|
0.362
|
||
Tubulin B3
|
5.4
|
10.6
|
0.349
|
4.9
|
3.9
|
0.419
|
||
CD4
|
8.6
|
3.6
|
0.946
|
4.9
|
2.8
|
0.81
|
||
CD8
|
8.6
|
15.4
|
0.919
|
4.9
|
3.9
|
0.924
|
||
SNPs
|
||||||||
MDR1 C3435T
|
CC
|
TT
|
CT
|
P-value
|
CC
|
TT
|
CT
|
P-value
|
13.5
|
15.4
|
8.2
|
0.318
|
8.5
|
4.9
|
2.8
|
0.374
|
|
MDR1 G2677 T
|
GG
|
TT
|
GT
|
GG
|
TT
|
GT
|
||
8.2
|
3.6
|
15.4
|
0.104
|
3.9
|
2.8
|
12
|
0.041
|
|
ERCC1C8092A
|
AA
|
CC
|
CA
|
AA
|
CC
|
CA
|
||
3.6
|
8.6
|
15.4
|
0.14
|
0.9
|
3.9
|
5.1
|
0.008
|
|
ERCC1 N118 N
|
CC
|
TT
|
CT
|
CC
|
TT
|
CT
|
||
8.2
|
10.6
|
8.5
|
0.394
|
5.1
|
6.4
|
3.9
|
0.195
|