Introduction
Materials and methods
Patients cohort
Immunostaining
Statistical analysis
Results
Study population
Study population divided into TRAP1-low and TRAP1-high | ||||
---|---|---|---|---|
N = 208 | TRAP1-low | TRAP1-high | ||
Characteristics | n = 93 (%) | n = 115 (%) | p | Adjusted p |
Age
| ||||
≤ 55 (n = 98) | 49 (23.6) | 49 (23.6) | ||
> 55 (n = 110) | 44 (21.2) | 66 (31.7) | 0.148 | |
Histology
| ||||
Serous (n = 183) | 76 (36.5) | 107 (51.4) | ||
Non-serous1 (n = 25) | 17 (8.2) | 8 (3.8) | 0.013 | 0.078 |
FIGO
| ||||
II (n = 9) | 5 (2.4) | 4 (1.9) | ||
III (n = 164) | 70 (33.6) | 94 (45.2) | 0.5262 | |
IV (n = 35) | 18 (8.7) | 17 (8.2) | ||
Grade (1missing) | ||||
Grade 1&2 (n = 55) | 19 (9.2) | 36 (17.4) | ||
Grade 3 (n = 152) | 73 (35.3) | 79 (38.2) | 0.087 | |
Residual tumor
| ||||
no (n = 146) | 64 (30.8) | 82 (39.4) | ||
> 0 cm (n = 62) | 29 (13.9) | 33 (15.9) | 0.697 | |
Peritoneal Carcinomatosis
| ||||
no (n = 64) | 28 (13.5) | 36 (17.3) | ||
yes (n = 144) | 65 (31.5) | 79 (38.0) | 0.852 |
Immunohistochemical evaluation
N = 208 | ERα- | ERα+ | ||
---|---|---|---|---|
Characteristics | n = 99 (%) | n = 109 (%) | p | Adjusted p |
Age
| ||||
≤ 55 (n = 98) | 55 (26.4) | 43 (20.7) | ||
> 55 (n = 110) | 44 (21.2) | 66 (31.7) | 0.026 | 0.080 |
Histology
| ||||
Serous (n = 183) | 81 (38.9) | 102 (49.0) | ||
Non-serous1 (n = 25) | 18 (8.7) | 7 (3.4) | 0.009 |
0.045
|
FIGO
2
| ||||
II (n = 9) | 3 (1.4) | 6 (2.9) | ||
III (n = 164) | 76 (33.6) | 88 (42.3) | 0.1582 | |
IV (n = 35) | 20 (9.6) | 15 (7.2) | ||
Grade (1 missing) | ||||
Grade 1&2 (n = 55) | 18 (8.7) | 37 (17.9) | ||
Grade 3 (n = 152) | 81 (39.1) | 71 (34.3) | 0.009 | 0.054 |
Residual tumor
| ||||
no (n = 146) | 66 (31.7) | 80 (38.5) | ||
> 0 cm (n = 62) | 33 (15.9) | 29 (13.9) | 0.289 | |
Peritoneal Carcinomatosis
| ||||
no (n = 64) | 31 (14.9) | 33 (15.9) | ||
yes (n = 144) | 68 (32.7) | 76 (36.5) | 0.871 |
Relevance of ERα and TRAP1 expression for chemotherapy response and patients’ survival
A) Overall survival | ||||||||
---|---|---|---|---|---|---|---|---|
N = 208 | Univariate | Multivariate | ||||||
ERα | TRAP1 | Combination | ||||||
Characteristics | HR (CI95%) | p | HR (CI95%) | p | HR (CI95%) | p | HR (CI 95%) | p |
Age (per decade) |
1.44 (1.21-1.71)
|
<0.001
|
1.40 (1.17-1.68)
|
<0.001
|
1.42 (1.18-1.71)
|
<0.001
|
1.50 (1.24-1.82)
|
<0.001
|
Histology (non-serous vs serous) | 1.05 (0.57-1.92) | 0.874 | 1.20 (0.64-2.27) | 0.555 | 1.22 0.65-2.29) | 0.545 | 1.33 (0.70-2.52) | 0.381 |
FIGO (IV vs III vs II) | 1.96 (1.25-3.06) | 0.003 | 1.39 (0.85-2.25) | 0.187 | 1.38 (0.85-2.24) | 0.188 | 1.39 (0.86-2.27) | 0.176 |
Grade (3 vs 1,2) | 1.74 (1.05-2.88) | 0.032 | 0.98 (0.58-1.67) | 0.951 | 1.34 (0.67-1.92) | 0.631 | 0.96 (0.57-1.64) | 0.893 |
Residual tumor (yes vs no) |
2.35 (1.54-3.61)
|
<0.001
|
1.87 (1.21-2.89)
|
0.005
|
1.79 (1.16-2.77)
|
0.009
|
1.80 (1.17-2.78)
|
0.008
|
Peritoneal Carcinomatosis (yes vs no) |
3.01 (1.75-5.16)
|
<0.001
|
2.75 (1.56-4.84)
|
<0.001
|
2.45 (1.38-4.32)
|
0.002
|
2.68 (1.51-4.74)
|
0.001
|
ERα (1/2/3 vs 0) |
0.56 (0.37-0.84)
|
0.005
|
0.51 (0.34-0.77)
|
0.002
| ||||
TRAP1 (3 vs 0/1/2)
|
0.63 (0.42-0.94)
|
0.025
|
0.65 (0.43-0.99)
|
0.044
| ||||
Combination ERα/TRAP1* |
0.49 (0.32-0.75)
|
0.001
|
0.41 (0.27-0.64)
|
<0.001
| ||||
B) Progression free survival
| ||||||||
Characteristics
|
HR (CI95%)
|
p
|
HR (CI95%)
|
p
|
HR (CI95%)
|
p
|
HR (CI 95%)
|
p
|
Age (per decade) |
1.21 (1.06-1.38)
|
0.041
| 1.14 (0.99-1.31) | 0.056 | 1.15 (1.00-1.32) | 0.055 |
1.17 (1.02-1.35)
|
0.027
|
Histology (non-serous vs serous) | 0.91 (0.55-1.49) | 0.701 | 1.23 (0.72-2.11) | 0.453 | 1.25 (0.73-2.15) | 0.416 | 1.25 (0.72-2.14) | 0.428 |
FIGO (IV vs III vs II) |
2.48 (1.69-3.62)
|
<0.001
|
1.85 (1.22-2.79)
|
0.004
|
1.91 (1.26-2.89)
|
0.002
|
1.91 (1.26-2.89)
|
0.002
|
Grade (3 vs 1,2) |
1.49 (1.03-2.17)
|
0.035
| 0.93 (0.62-1.39) | 0.721 | 0.95 (0.64-1.41) | 0.794 | 0.89 (0.59-1.33) | 0.559 |
Residual tumor yes vs no) |
1.99 (1.45-2.75)
|
<0.001
|
1.56 (1.11-2.18)
|
0.010
|
1.55 (1.10-2.17)
|
0.011
|
1.56 (1.11-2.18)
|
0.010
|
Peritoneal Carcinomatosis (yes vs no) |
2.96 (2.01-4.37)
|
<0.001
|
2.98 (1.95-4.55)
|
<0.001
|
2.92 (1.91-4.47)
|
<0.001
|
3.00 (1.96-4.60)
|
<0.001
|
ERα (1/2/3 vs 0) | 0.84 (0.62-1.15) | 0.279 | 0.80 (0.58-1.11) | 0.185 | ||||
TRAP1 (3 vs 0/1/2) | 0.87 (0.63-1.18) | 0.367 | 0.87 (0.63-1.20) | 0.398 | ||||
Combination ERα/TRAP1* | 0.79 (0.56-1.12) | 0.188 | 0.70 (0.48-1.02) | 0.061 | ||||
C) Chemotherapy response
| ||||||||
Characteristics
|
HR (CI95%)
|
p
|
HR (CI95%)
|
p
|
HR (CI95%)
|
p
|
HR (CI 95%)
|
p
|
Age (per decade) |
1.33 (1.02-1.74)
|
0.036
|
1.42 (1.06-1.9)
|
0.019
|
1.43 (1.06-1.91)
|
0.019
|
1.57 (1.15-2.15)
|
0.005
|
Histology (non-serous vs serous) | 0.74 (0.26-2.08) | 0.567 | 0.92 (0.30-2.83) | 0.889 | 0.93 (0.30-2.83) | 0.893 | 0.88 (0.28-2.73) | 0.824 |
FIGO (IV vs III vs II) |
2.06 (1.02-4.15)
|
0.044
| 1.59 (0.73-3.49) | 0.241 | 1.65 (0.76-3.61) | 0.207 | 1.67 (0.75-3.72) | 0.205 |
Grade (3 vs 1,2) | 1.17 (0.56-2.44) | 0.683 | 0.72 (0.32-1.64) | 0.437 | 0.76 (0.33-1.72) | 0.505 | 0.56 (0.23-1.33) | 0.188 |
Residual tumor (yes vs no) |
1.96 (1.01-3.80)
|
0.046
| 1.35 (0.67-2.75) | 0.411 | 1.43 (0.71-2.91) | 0.318 | 1.36 (0.66-2.81) | 0.408 |
Peritoneal Carcinomatosis (yes vs no) |
3.01 (1.32-6.85)
|
0.009
|
3.04 (1.25-7.36)
|
0.014
|
2.89 (1.19-7.01)
|
0.018
|
3.34 (1.34-8.36)
|
0.009
|
ERα (1/2/3 vs 0) | 0.62 (0.33-1.17) | 0.138 | 0.53 (0.26-1.06) | 0.071 | ||||
TRAP1 (3 vs 0/1/2) |
0.53 (0.28-1.00)
|
0.050
|
0.48 (0.24-0.96)
|
0.037
| ||||
Combination ERα/TRAP1* |
0.38 (0.19-0.75)
|
0.005
|
0.24 (0.11-0.54)
|
< 0.001
|