Fig. 1Immunohistochemistry findings showing epithelial protein loss/alteration (A, B, D, E) and mesenchymal protein expression (C, F) in an adenocarcinoma of the lung. (A) Normal membranous expression of E-cadherin. (B) Normal membranous expression of β-catenin. (C) Normal negative vimentin expression. (D) Membranous E-cadherin loss. (E) Aberrant cytoplasmic expression of β-catenin. (F) Aberrant cytoplasmic vimentin expression.
Fig. 2Survival curves based on the expression of two epithelial-mesenchymal transition-related proteins and their combination using the Kaplan-Meier method with the log-rank test.
Table 1.Clinicopatholgic findings associated with the expression of EMT proteins
Characteristics |
No. of examined |
E-Cadherin
|
p-value |
β-Catenin
|
p-value |
Vimentin
|
p-value |
Negative |
Expression |
Aberrant expression |
Normal |
Expression |
Normal |
Total |
193 (100) |
|
|
|
|
|
|
|
|
|
Sex |
|
|
|
|
|
|
|
|
|
|
Male |
90 (46.6) |
20 (22.2) |
70 (77.8) |
0.084 |
71 (78.9) |
19 (21.1) |
0.489 |
27 (30.0) |
63 (70.0) |
0.282 |
Female |
103 (53.3) |
14 (13.6) |
89 (86.4) |
|
80 (77.7) |
23 (22.3) |
|
26 (25.2) |
77 (74.8) |
|
Age (yr) |
|
|
|
|
|
|
|
|
|
|
≤ 65 |
79 (40.9) |
12 (15.2) |
67 (84.8) |
0.295 |
60 (75.9) |
19 (24.1) |
0.32 |
23 (29.1) |
56 (70.9) |
0.394 |
> 65 |
114 (59.1) |
22 (19.3) |
92 (80.7) |
|
91 (79.8) |
23 (20.2) |
|
30 (26.3) |
84 (73.7) |
|
Smoking history |
|
|
|
|
|
|
|
|
|
|
No |
115 (59.6) |
15 (13.0) |
100 (87.0) |
0.034*
|
92 (80.0) |
23 (20.0) |
0.292 |
33 (28.7) |
82 (71.3) |
0.383 |
Yes |
78 (40.4) |
19 (24.4) |
59 (75.9) |
|
59 (75.6) |
19 (24.4) |
|
20 (25.6) |
58 (74.4) |
|
Tumor size (cm) |
|
|
|
|
|
|
|
|
|
|
≤ 3 |
127 (65.8) |
17 (13.4) |
110 (86.6) |
0.028*
|
92 (72.4) |
35 (27.6) |
0.004*
|
32 (25.2) |
95 (74.8) |
0.209 |
> 3 |
66 (34.2) |
17 (25.8) |
49 (74.2) |
|
59 (89.4) |
7 (10.6) |
|
21 (31.8) |
45 (68.2) |
|
Pleural invasion |
|
|
|
|
|
|
|
|
|
|
Absent |
132 (67.9) |
17 (13.0) |
114 (87.0) |
0.013*
|
93 (71.0) |
38 (29.0) |
<0.001*
|
29 (22.1) |
102 (77.9) |
0.014*
|
Present |
62 P2.1) |
17 (27.4) |
45 (72.6) |
|
58 (93.5) |
4 (6.5) |
|
24 (38.7) |
38 (61.3) |
|
Lymphatic invasion |
|
|
|
|
|
|
|
|
|
|
Absent |
124 (64.2) |
18 (14.5) |
106 (85.5) |
0.095 |
88 (71.0) |
36 (29.0) |
0.001*
|
31 (25.0) |
93 (75.0) |
0.195 |
Present |
69 (35.8) |
16 (23.2) |
53 (76.8) |
|
63 (91.3) |
6 (8.7) |
|
22 (31.9) |
47 (68.1) |
|
Vascular invasion |
|
|
|
|
|
|
|
|
|
|
Absent |
174 (90.2) |
27 (15.5) |
147 (84.5) |
0.029*
|
133 (76.4) |
41 (23.6) |
0.051 |
48 (27.6) |
126 (72.4) |
0.573 |
Present |
19 (9.8) |
7 (36.8) |
12 (63.2) |
|
18 (94.7) |
1 (5.3) |
|
5 (26.3) |
14 (73.7) |
|
Stage |
|
|
|
|
|
|
|
|
|
|
I |
126 (65.3) |
17 (13.5) |
109 (86.5) |
0.023*
|
88 (69.8) |
38 (30.2) |
<0.001*
|
33 (26.2) |
93 (73.8) |
0.921 |
II |
23 (11.9) |
4 (17.4) |
19 (82.6) |
|
20 (87.0) |
3 (13.0) |
|
9 P9.1) |
14 (60.9) |
|
III |
44 (22.8) |
13 (29.5) |
31 (70.55) |
|
43 (97.7) |
1 (2.3) |
|
11 (25.0) |
33 (75.0) |
|
Table 2.Correlation coefficients of expression status between three epithelial-mesenchymal transition proteins
|
Correlation coefficients ρ (n = 193)
|
|
E-Cadherin |
β-Catenin |
Vimentin |
E-Cadherin |
1 |
0.145*
|
-0.051 |
β-Catenin |
|
1 |
-0.24*
|
Vimentin |
|
|
1 |
Table 3.Clinicopathologic findings associated with the altered expression of cadherin-catenin complex
Characteristics |
No. of examined |
Altered caherin-catenin complex
|
Alteration |
Normal |
p-value |
Total |
193 (100) |
|
|
|
Sex |
|
|
|
|
Male |
90 (46.6) |
18 (20.0) |
72 (80.05) |
0.116 |
Female |
103 (53.3) |
13 (12.6) |
90 (87.4) |
|
Age (yr) |
|
|
|
|
≤ 65 |
79 (40.9) |
11 (13.9) |
68 (86.1) |
0.32 |
> 65 |
114 (59.1) |
20 (17.5) |
94 (82.5) |
|
Smoking history |
|
|
|
|
No |
115 (59.6) |
13 (11.3) |
102 (88.7) |
0.024*
|
Yes |
78 (40.4) |
18 (23.1) |
60 (76.9) |
|
Tumor size (cm) |
|
|
|
|
≤ 3 |
127 (65.8) |
15 (11.8) |
112 (88.2) |
0.023*
|
> 3 |
66 (34.2) |
16 (24.2) |
50 (75.8) |
|
Pleural invasion |
|
|
|
|
Absent |
132 (67.9) |
16 (12.2) |
115 (87.8) |
0.030*
|
Present |
62 (32.1) |
15 (24.2) |
47 (75.8) |
|
Lymphatic invasion |
|
|
|
|
Absent |
124 (64.2) |
16 (12.9) |
108 (87.1) |
0.083 |
Present |
69 (35.8) |
15 (21.7) |
54 (78.3) |
|
Vascular invasion |
|
|
|
|
Absent |
174 (90.2) |
25 (14.4) |
149 (85.6) |
0.061 |
Present |
19 (9.8) |
6 (31.6) |
13 (68.4) |
|
Stage |
|
|
|
|
I |
126 (65.3) |
15 (11.9) |
111 (88.1) |
|
II |
23 (11.9) |
4 (17.4) |
19 (82.6) |
0.020*
|
III |
44 (22.8) |
12 (27.3) |
32 (72.7) |
|
Table 4.Correlation of histologic subtypes and two EMT protein expressions
Predominant subtype of adenocarcinoma |
Altered cadherin-catenin complex
|
Alteration |
Normal |
p-value |
Acinar predominant |
25 (17.9) |
115 (82.1) |
>0.05 |
Papillary predominant |
1 (16.7) |
5 (83.3) |
|
Lepidic predominant |
2 (7.7) |
24 (92.3) |
|
Solid predominant |
3 (16.7) |
15 (83.3) |
|
Micropapillary predominant |
0 |
2 (100) |
|
Invasive mucinous adenocarcinoma |
0 |
1 (100) |
|
Table 5.Multivariate analysis of predictive factors for disease-free survival (Cox proportional hazards model)
Prognostic factors |
Hazard ratio (95% CI) |
p-value |
Cadherin-catenin complex |
1.926 (1.119-3.314) |
0.018*
|
Alteration vs normal |
|
|
Pleural invasion |
|
|
Present vs absent |
1.071 (0.942-1.513) |
0.458 |
Pathologic stage |
|
|
II vs I |
2.928 (1.387-6.183) |
0.005*
|
III vs I |
6.034 (3.292-11.060) |
< 0.001*
|