Fig. 1Expression of TWIST, hypoxia-inducible factor 1α (HIF1α), p53, and E-cadherin in ovarian epithelial cancer. TWIST (A, clear cell carcinoma), HIF1α (B, mucinous carcinoma), and p53 (C, serous carcinoma) are expressed in the nuclei of tumor cells, whereas E-cadherin (D, clear cell carcinoma) expression is lost.
Fig. 2Kaplan-Meier analysis of overall survival (OS) and progression-free survival (PFS) in ovarian epithelial cancer according to the immunoexpression of TWIST. TWIST expression is associated with poorer OS and PFS.
Table 1.Clinicopathological features of the ovarian epithelial cancer patients
Parameter |
|
n (%) (n = 123) |
Histologic type |
Serous |
63 (51.2) |
|
Mucinous |
24 (19.5) |
|
Endometrioid |
11 (8.9) |
|
Clear cell |
25 (20.4) |
Histologic grade |
Well differentiated (G1) |
35 (28.5) |
|
Moderately differentiated (G2) |
62 (50.4) |
|
Poorly differentiated (G3) |
26 (21.1) |
Nuclear grade |
1 |
13 (10.6) |
|
2 |
62 (50.4) |
|
3 |
48 (39.0) |
Mitoses |
< 10/10 HPF |
52 (42.3) |
|
10–19/10 HPF |
41 (33.3) |
|
≥ 20/10 HPF |
30 (24.4) |
Size (cm) |
< 10 |
58 (47.2) |
|
≥ 10 |
65 (52.8) |
FIGO stage |
I |
55 (44.7) |
|
II |
8 (6.5) |
|
III |
43 (35.0) |
|
IV |
17 (13.8) |
Disease progression |
No |
63 (51.2) |
|
Yes |
60 (48.8) |
Overall survival |
Alive |
73 (59.3) |
|
DOD |
50 (40.7) |
Table 2.Relationship between TWIST, HIF1α, p53, and E-cadherin with clinicopathological factors in patients with OEC (n=123)
Parameter |
n (%) |
TWIST expression |
HIF1α expression |
p53 expression |
E-Cadherin reduced expression |
Histologic type |
|
|
|
|
|
Serous |
63 (51.2) |
15 (23.8) |
16 (25.4) |
28 (44.4) |
28 (44.4) |
Mucinous |
24 (19.5) |
7 (29.2) |
13 (54.2) |
3 (12.5) |
16 (66.7) |
Endometrioid |
11 (8.9) |
2 (18.2) |
0 (0) |
4 (36.4) |
6 (58.3) |
Clear cell |
25 (20.4) |
11 (44.0) |
14 (55.0) |
1 (4.0) |
13 (52.0) |
p-value |
|
.240 |
.001 |
.000 |
.320 |
Histologic grade |
|
|
|
|
|
G1 |
35 (28.5) |
9 (25.7) |
15 (42.9) |
1 (2.9) |
20 (57.1) |
G2 |
62 (50.4) |
12 (19.4) |
18 (29.0) |
23 (37.1) |
35 (56.5) |
G3 |
26 (21.1) |
14 (53.8) |
10 (48.5) |
12 (46.2) |
8 (31.8) |
p-value |
|
.004 |
.357 |
.000 |
.063 |
Nuclear grade |
|
|
|
|
|
1 |
13 (10.6) |
3 (23.1) |
4 (30.8) |
2 (15.4) |
6 (46.2) |
2 |
62 (50.4) |
15 (24.2) |
19 (30.7) |
19 (30.6) |
30 (48.4) |
3 |
48 (39.0) |
17 (35.4) |
20 (41.7) |
15 (31.2) |
27 (56.2) |
p-value |
|
.391 |
.459 |
.507 |
.664 |
Mitoses |
|
|
|
|
|
< 10 |
52 (42.3) |
16 (29.4) |
23 (43.1) |
3 (4.0) |
29 (54.9) |
10-19 |
41 (33.3) |
11 (28.6) |
13 (33.3) |
16 (39.0) |
22 (54.8) |
≥ 20 |
30 (24.4) |
8 (23.3) |
7 (23.3) |
17 (56.7) |
12 (40.0) |
p-value |
|
.888 |
.139 |
.000 |
.361 |
Tumor size (cm) |
|
|
|
|
|
< 10 |
58 (47.2) |
14 (24.1) |
16 (27.6) |
19 (32.8) |
27 (46.6) |
≥ 10 |
65 (52.8) |
21 (32.3) |
27 (41.5) |
17 (26.2) |
36 (55.4) |
p-value |
|
.424 |
.131 |
.435 |
.369 |
FIGO stage |
|
|
|
|
|
Early (I, II) |
63 (51.2) |
15 (23.8) |
25 (39.7) |
7 (11.1) |
41 (65.1) |
Advanced (III, IV) |
60 (48.8) |
20 (33.3) |
18 (30.0) |
29 (48.3) |
22 (36.7) |
p-value |
|
.318 |
.344 |
.000 |
.002 |
Total |
123 |
35 (28.5) |
43 (35.0) |
36 (29.3) |
60 (48.8) |
Table 3.Correlation between TWIST, HIF1α, p53, and E-cadherin
|
|
TWIST |
E-cadherin |
HIF1α |
p53 |
TWIST |
p-value |
- |
.000 |
.000 |
.142 |
|
c.c |
- |
– 0.309 |
0.532 |
0.168 |
E-Cadherin |
p-value |
- |
- |
.322 |
.041 |
|
c.c |
- |
- |
– 0.157 |
– 0.219 |
HIF1α |
p-value |
- |
- |
- |
.611 |
|
c.c |
- |
- |
- |
– 0.006 |
Table 4.Univariate analysis of various clinicopathological parameters and the immunoexpression of TWIST, HIF1α, p53, and E-cadherin in relation to overall survival (OS) and progression-free survival (PFS)
|
OS
|
PFS
|
|
Alive (n = 73) |
DOD (n = 50) |
p-value |
Progression-free (n = 63) |
Progression (n = 60) |
p-value |
Histologic type |
|
|
.327 |
|
|
.000 |
Serous |
35 (55.6) |
28 (44.4) |
|
21 (33.3) |
42 (66.7) |
|
Mucinous |
18 (75.0) |
6 (25.0) |
|
19 (79.2) |
5 (20.8) |
|
Endometrioid |
7 (63.6) |
4 (36.4) |
|
7 (63.6) |
4 (36.4) |
|
Clear |
13 (52.0) |
12 (48.0) |
|
16 (64.0) |
9 (36.0) |
|
Histologic grade |
|
|
.030 |
|
|
.000 |
Well differentiated |
27 (77.1) |
8 (22.9) |
|
28 (80.0) |
7 (20.0) |
|
Moderately differentiated |
34 (54.8) |
28 (45.2) |
|
28 (45.2) |
34 (54.8) |
|
Poorly differentiated |
12 (46.2) |
14 (53.8) |
|
7 (26.9) |
19 (73.1) |
|
Nuclear grade |
|
|
.155 |
|
|
.071 |
1 |
10 (76.9) |
3 (23.1) |
|
10 (76.9) |
3 (23.1) |
|
2 |
39 (62.9) |
23 (37.1) |
|
33 (53.2) |
29 (46.8) |
|
3 |
24 (50.0) |
24 (50.0) |
|
20 (41.7) |
28 (58.3) |
|
Mitoses |
|
|
.029 |
|
|
.027 |
≤ 10/10 HPF |
37 (72.5) |
15 (27.5) |
|
34 (65.4) |
18 (34.6) |
|
> 10 and ≤ 20/10 HPF |
18 (43.9) |
23 (56.1) |
|
17 (41.5) |
24 (58.5) |
|
> 20/10 HPF |
18 (60.0) |
12 (40.0) |
|
12 (40.0) |
18 (60.0) |
|
Tumor size (cm) |
|
|
.141 |
|
|
.002 |
< 10 |
30 (51.7) |
28 (48.3) |
|
21 (36.2) |
37 (63.8) |
|
≥ 10 |
43 (66.2) |
22 (33.8) |
|
42 (64.6) |
23 (35.4) |
|
FIGO stage |
|
|
.000 |
|
|
.000 |
I – II |
52 (82.5) |
11 (17.5) |
|
56 (88.9) |
7 (11.1) |
|
III – IV |
21 (35.0) |
39 (65.0) |
|
7 (11.7) |
53 (88.3) |
|
TWIST expression |
|
|
.001 |
|
|
.027 |
No |
61 (69.3) |
27 (30.7) |
|
51 (58.0) |
37 (42.0) |
|
Yes |
12 (34.3) |
23 (65.7) |
|
12 (34.3) |
23 (65.7) |
|
E-Cadherin |
|
|
.000 |
|
|
.001 |
No |
22 (36.7) |
38 (63.3) |
|
21 (35.0) |
39 (65.0) |
|
Yes |
51 (81.0) |
12 (19.0) |
|
42 (66.7) |
21 (33.3) |
|
HIF1α expression |
|
|
.185 |
|
|
.850 |
No |
51 (63.8) |
29 (36.2) |
|
40 (50.0) |
40 (50.0) |
|
Yes |
22 (51.2) |
21 (48.8) |
|
23 (53.5) |
20 (46.5) |
|
p53 expression |
|
|
.004 |
|
|
.000 |
No |
59 (67.8) |
28 (32.2) |
|
56 (64.4) |
31 (35.6) |
|
Yes |
14 (38.9) |
22 (61.1) |
|
7 (19.4) |
29 (80.6) |
|
TWIST/E-cadherin |
|
|
.003 |
|
|
.127 |
No |
64 (66.7) |
32 (33.3) |
|
53 (55.2) |
43 (44.8) |
|
Yes |
9 (33.3) |
18 (66.7) |
|
10 (37.0) |
17 (63.0) |
|
TWIST/p53 |
|
|
.082 |
|
|
.000 |
No |
68 (61.3) |
41 (38.7) |
|
62 (56.9) |
47 (43.1) |
|
Yes |
5 (35.7) |
9 (64.3) |
|
1 (7.1) |
13 (92.9) |
|
HIF1α/TWIST/E-cadherin expression |
|
|
.011 |
|
|
.459 |
No |
67 (64.4) |
37 (35.6) |
|
55 (52.9) |
49 (47.1) |
|
Yes |
6 (31.6) |
13 (68.4) |
|
8 (42.1) |
11 (57.9) |
|
Table 5.Multivariate analysis of several clinicopathological factors in relation to the OS of patients with OEC
Variables |
Grouping |
p-value |
Hazard ratio |
95% of CI |
Histologic grade |
I vs II – IV |
.862 |
0.672 |
0.216 – 2.091 |
FIGO stage |
I, II vs III, IV |
.003 |
0.306 |
0.140 – 0.670 |
Mitoses |
Low vs high |
.268 |
1.853 |
0.833 – 4.121 |
TWIST expression |
No vs yes |
.000 |
0.061 |
0.013 – 0.278 |
p53 expression |
No vs yes |
.490 |
0.788 |
0.400 – 1.550 |
TWIST/E-cadherin |
No vs yes |
.054 |
5.457 |
0.971 – 30.657 |
HIF1a/TWIST/E-cadherin |
No vs yes |
.860 |
1.178 |
0.190 – 7.312 |