Fig. 1Various immunohistochemical expression levels of mitotic arrest deficiency protein 2 (MAD2) in ovarian serous carcinoma are demonstrated. MAD2 score 1 (A), MAD2 score 2 (B), MAD2 score 3 (C), and MAD2 score 4 (D).
Fig. 2Nuclear membranous staining pattern in ovarian endometrioid carcinoma (A), and cytoplasmic staining pattern in ovarian mucinous carcinoma (B). (C, D) In ovarian mucinous carcinoma, heterogeneous staining pattern is commonly observed. High-level mitotic arrest deficiency protein 2 (MAD2) expression and low-level MAD2 expression coexist in the same tumor.
Fig. 3Kaplan-Meier survival curves show a significant correlation between high or low expression levels of mitotic arrest deficiency protein 2 (MAD2) and progression-free survival in high-grade serous carcinoma (p=.04).
Table 1.Associations between MAD2 expression and clinicopathologic features in patients with ovarian carcinoma
Variable |
No. of cases (n = 85) |
MAD2 expression
|
p-value |
MAD2-La (n = 40, 47.1%) |
MAD2-Hb (n = 45, 52.9%) |
Age (yr) |
|
|
|
|
< 60 |
59 (69.4) |
30 (35.3) |
29 (34.1) |
.29 |
≥ 60 |
26 (30.6) |
10 (11.8) |
16 (18.8) |
|
Stagec
|
|
|
|
|
I, II |
42 (49.4) |
20 (23.5) |
22 (25.9) |
.92 |
III, IV |
43 (50.6) |
20 (23.5) |
23 (27.1) |
|
Type I tumors |
44 (51.8) |
23 (27.1) |
21 (24.7) |
.32 |
Low-grade serous CA |
7 (8.2) |
6 (7.1) |
1 (1.2) |
|
Low-grade endometrioid CA |
8 (9.4) |
2 (2.4) |
6 (7.1) |
|
Clear cell CA |
10 (11.8) |
7 (8.2) |
3 (3.5) |
|
Mucinous CA |
19 (22.4) |
8 (9.4) |
11 (12.9) |
|
Type II tumors |
41 (48.2) |
17 (20.0) |
24 (28.2) |
|
High-grade serous CA |
37 (43.5) |
14 (16.5) |
23 (27.1) |
|
High-grade endometrioid CA |
2 (2.4) |
2 (2.4) |
0 (0) |
|
Transitional cell CA |
2 (2.4) |
1 (1.2) |
1 (1.2) |
|
p53 expression |
|
|
|
|
positive |
42 (49.4) |
16 (18.8) |
26 (30.6) |
.1 |
negative |
43 (50.6) |
24 (28.2) |
19 (22.4) |
|
Serous CA (n = 44) |
|
|
|
|
Low-grade serous CA |
7 (15.9) |
6 (13.6) |
1 (2.3) |
.035d
|
High-grade serous CA |
37 (84.1) |
14 (31.8) |
23 (52.3) |
|
Table 2.Associations between p53 expression and clinicopathologic features in patients with ovarian carcinoma
Variable |
No. of cases (n = 85) |
p53 expression
|
p-value |
Positive (n = 42, 49.4%) |
Negative (n = 43, 50.6%) |
Age (yr) |
|
|
|
|
< 60 |
59 (69.4) |
29 (34.1) |
30 (35.3) |
.94 |
≥ 60 |
26 (30.6) |
13 (15.3) |
13 (15.3) |
|
Stagea
|
|
|
|
|
I, II |
42 (49.4) |
16 (18.8) |
26 (30.6) |
.039b
|
III, IV |
43 (50.6) |
26 (30.6) |
17 (20.0) |
|
Type I tumors |
44 (51.8) |
15 (17.6) |
29 (34.1) |
.003b
|
Low-grade serous CA |
7 (8.2) |
1 (1.2) |
6 (7.1) |
|
Low-grade endometrioid CA |
8 (9.4) |
1 (1.2) |
7 (8.2) |
|
Clear cell CA |
10 (11.8) |
2 (2.4) |
8 (9.4) |
|
Mucinous CA |
19 (22.4) |
11 (12.9) |
8 (9.4) |
|
Type II tumors |
41 (48.2) |
27 (31.8) |
14 (16.5) |
|
High-grade serous CA |
37 (43.5) |
25 (29.4) |
12 (14.1) |
|
High-grade endometrioid CA |
2 (2.4) |
1 (1.2) |
1 (1.2) |
|
Transitional cell CA |
2 (2.4) |
1 (1.2) |
1 (1.2) |
|
Serous CA (n = 44) |
|
|
|
|
Low-grade serous CA |
7 (15.9) |
1 (2.3) |
6 (13.6) |
.013b
|
High-grade serous CA |
37 (84.1) |
25 (56.8) |
12 (27.3) |
|
Table 3.Prognostic factors in Cox's proportional hazard model in ovarian carcinoma
Variables |
Hazard ratio (univariate CI) |
p-value |
Hazard ratio (multivariate CI) |
p-value |
Age (yr) |
|
|
|
|
≥ 60/ < 60 |
5.340 (1.578-18.066) |
.007c
|
4.407 (1.261-15.406) |
.02c
|
Stage |
|
|
|
|
III, IV/I, II |
5.773 (1.241-26.858) |
.025c
|
2.989 (0.556-16.081) |
.2 |
Ovarian CA type |
|
|
|
|
Type II/type I |
4.110 (1.087-15.541) |
.037c
|
2.539 (0.565-11.410) |
.22 |
MAD2 expression |
|
|
|
|
MAD2-La/MAD2-Hb
|
2.456 (0.651-9.265) |
.19 |
3.826 (0.915-16.000) |
.07 |
p53 expression |
|
|
|
|
Positive/negative |
1.373 (0.418-4.510) |
.6 |
1.308 (0.361-4.737) |
.68 |
Table 4.Prognostic factors in Cox's proportional hazard model in ovarian high-grade serous carcinoma
Variable |
Hazard ratio (multivariate CI) |
p-value |
Age (yr) |
|
|
≥ 60/ < 60 |
6.272 (1.054-37.328) |
.044c
|
Stage |
|
|
III, IV/I, II |
3.982 (0.334-47.542) |
.28 |
MAD2 expression |
|
|
MAD2-La/MAD2-Hb
|
27.970 (1.838-425.629) |
.016c
|
Debulking surgery |
|
|
suboptimal/optimal |
36.458 (1.979-671.739) |
.016c
|