Fig. 1Naked cuticle Drosophila 1 (NKD1) is expressed in normal bronchial epithelium and alveolar cells, with scores ranging from 3 to 6 (mean, 4.3) where (A) is a score of 3, (B) is a score of 5, and (C) is a score of 6.
Fig. 2Immunohistochemical findings of naked cuticle Drosophila 1 (NKD1) in histologic subtypes of lung adenocarcinoma. (A, B) Reduced NKD1 expression is observed in the solid predominant type. (C, D) Normal expression of NKD1 in the lepidic predominant type. (E, F) Overexpression in the papillary predominant type.
Fig. 3Cumulative disease-free survival rates of patients according to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and small adenocarcinoma (SAD). AIS vs SAD, p=0.453; MIA vs SAD, p=0.296 (log-rank test).
Table 1.Relationship between histologic subtypes and clinicopathologic factors
|
AIS (n = 5) |
MIA (n = 8) |
SAD (n = 27) |
Mean age (range, yr) |
55.4 (49-60) |
58.5 (43-76) |
60.9 (30-79) |
Gender (male/female) |
3/2 |
3/5 |
12/15 |
Smoking status |
|
|
|
Never-smoker |
3 |
6 |
20 |
Ever-smoker |
2 |
2 |
7 |
Gross size (mean) |
0.9 ± 0.2 (0.7) |
1.05 ± 1.05 (0.83) |
1.35 ± 0.65 (1.42) |
Invasive size (mean) |
0 |
0.3 ± 0.15 (0.4) |
1.35 ± 0.65 (1.37) |
Predominant invasive pattern |
|
|
|
Acinar, papillary |
N/A |
6/2 |
19/4 |
Micropapillary |
N/A |
0 |
0 |
Solid |
N/A |
0 |
4 |
Nodal metastasis |
|
|
|
Yes |
0 |
0 |
2 |
No |
2 |
6 |
24 |
Not available |
3 |
2 |
1 |
Lymphatic invasion |
0 |
0 |
1 |
Tumor necrosis |
0 |
0 |
1 |
Follow-up |
|
|
|
Mean time (mo) |
28.2 |
35.0 |
35.6 |
Range time (mo) |
11-68 |
13-45 |
1-156 |
DOD |
0 |
0 |
3a
|
AFD |
5 |
8 |
23 |
Table 2.Clinicopathologic characteristics according to NKD1 expression
|
Total (n = 40) |
NKD1-reduced (n = 8) |
NKD1-normal (n = 15) |
NKD1-overexpressed (n = 17) |
p-value |
Age (yr) |
|
|
|
|
0.506 |
< 61 |
22 (100) |
3 (13.7) |
8 (36.3) |
11 (50) |
|
≥ 61 |
18 (100) |
5 (55.6) |
7 (38.9) |
6 (33.3) |
|
Gender |
|
|
|
|
0.075 |
Male |
17 (100) |
4 (23.5) |
3 (17.6) |
10 (58.8) |
|
Female |
23 (100) |
4 (17.3) |
12 (52.1) |
7 (30.4) |
|
Smoking status |
|
|
|
|
0.473 |
Never-smoker |
29 (100) |
5 (17.2) |
10 (34.5) |
14 (48.3) |
|
Ever-smoker |
11 (100) |
3 (27.2) |
5 (45.5) |
3 (27.3) |
|
Pathologic T stage status |
|
|
|
|
0.189 |
pTis |
5 (100) |
0 (0) |
4 (80) |
1 (20) |
|
pT1a |
35 (100) |
8 (22.9) |
11 (31.4) |
16 (45.7) |
|
Nodal metastasis |
|
|
|
|
0.003 |
Yes |
2 (100) |
2 (100) |
0 (0) |
0 (0) |
|
No |
32 (100) |
4 (12.5) |
11 (34.4) |
17 (53.1) |
|
N/A |
6 (100) |
2 (33.3) |
4 (66.6) |
0 (0) |
|
Histologic subtype |
|
|
|
|
0.409 |
AIS |
5 (100) |
0 (0) |
4 (80) |
1 (20) |
|
MIA |
8 (100) |
2 (25) |
3 (37.5) |
3 (37.5) |
|
SAD |
27 (100) |
6 (22.2) |
8 (29.6) |
13 (48.1) |
|
Predominant histologic pattern |
|
|
|
|
0.316 |
Lepidic |
13 (100) |
2 (15.4) |
7 (53.8) |
4 (30.8) |
|
Acinar |
19 (100) |
5 (26.3) |
6 (31.6) |
8 (42.1) |
|
Papillary |
4 (100) |
0 (0) |
0 (0) |
4 (100) |
|
Solid |
4 (100) |
1 (25) |
2 (50) |
1 (25) |
|
Table 3.Predominant histologic pattern according to NKD1 expression
|
Total (n = 40) |
NKD1-reduced (n = 8) |
NKD1-normal (n = 15) |
NKD1-overexpressed (n = 17) |
p-value |
Lepidic predominant |
13 (100) |
2 (15.4) |
7 (53.8) |
4 (30.8) |
0.347 |
Non-lepidic predominant |
27 (100) |
6 (22.2) |
8 (29.6) |
13 (48.1) |
|
Acinar predominant |
19 (100) |
5 (26.3) |
6 (31.6) |
7 (36.8) |
0.599 |
Non-acinar predominant |
21 (100) |
3 (14.3) |
9 (42.9) |
10 (47.6) |
|
Papillary predominant |
4 (100) |
0 (0) |
0 (0) |
4 (100) |
0.026 |
Non-papillary predominant |
36 (100) |
8 (22.9) |
15 (42.9) |
13 (34.3) |
|
Solid predominant |
4 (100) |
1 (25) |
2 (50) |
1 (25) |
0.821 |
Non-solid predominant |
36 (100) |
7 (19.4) |
13 (36.1) |
16 (44.4) |
|
Table 4.Univariate analysis of overall survival
Poor prognostic factors |
p-value |
Nodal metastasis |
0.001 |
Presence of micropapillary pattern |
0.001 |