Fig. 1Immunohistochemical results for sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), glioma-associated oncogene (Gli)-1, Gli-2, and Gli-3. (A) Shh immunostaining shows a strong cytoplasmic pattern in tumor cells. (B) Ptch is expressed in the cytoplasm of tumor cells. (C) Smo shows diffuse strong staining in the cytoplasm of tumor cells. (D) Gli-1 is expressed in the nucleus of tumor cells. (E) Gli-2 is expressed in a nuclear pattern. (F) Gli-3 is expressed in the nucleus of tumor cells (avidin-biotin-peroxidase complex staining).
Fig. 2Kaplan-Meier survival analysis in breast carcinoma. Patients with glioma-associated oncogene 2 (Gli-2) expression have a poor overall survival rate (p=0.012).
Table 1.Relationship between hedgehog related protein expression and the clinicopathologic factors of breast cancer
Clinicopathologic factors |
No. of cases (%) |
No. of positive cases (%)
|
Shh |
Ptch |
Smo |
Gli-1 |
Gli-2 |
Gli-3 |
Age (yr) |
|
|
|
|
|
|
|
< 50 |
179 (53.6) |
87 (48.6) |
100 (55.9) |
47 (26.3) |
77 (43.0) |
141 (78.8) |
99 (55.3) |
> 50 |
155 (46.4) |
77 (49.7) |
83 (53.5) |
28 (18.1) |
64 (41.3) |
111 (71.6) |
92 (59.4) |
p-value |
|
0.845 |
0.671 |
0.074 |
0.750 |
0.130 |
0.456 |
Size (cm) |
|
|
|
|
|
|
|
< 2 |
129 (38.6) |
60 (46.5) |
72 (55.8) |
30 (23.3) |
57 (44.2) |
95 (73.6) |
85 (65.9) |
2-5 |
172 (51.5) |
84 (48.8) |
91 (52.9) |
38 (22.1) |
71 (41.3) |
129 (75.0) |
93 (54.1) |
> 5 |
33 (9.9) |
20 (60.6) |
20 (60.6) |
7 (21.2) |
13 (39.4) |
28 (84.8) |
13 (39.4) |
p-value |
|
0.350 |
0.687 |
0.956 |
0.829 |
0.403 |
0.011*
|
Node metastasis |
|
|
|
|
|
|
|
0 |
179 (53.6) |
84 (46.9) |
96 (53.6) |
40 (22.3) |
80 (44.7) |
136 (76.0) |
111 (62.0) |
1-3 |
98 (29.3) |
40 (40.8) |
47 (48.0) |
18 (18.4) |
36 (36.7) |
74 (75.5) |
36 (36.7) |
> 4 |
57 (17.1) |
40 (70.2) |
40 (70.2) |
17 (29.8) |
25 (43.9) |
42 (73.7) |
44 (77.2) |
p-value |
|
0.001*
|
0.025*
|
0.257 |
0.423 |
0.940 |
0.000*
|
Stage |
|
|
|
|
|
|
|
I |
78 (23.4) |
32 (41.0) |
45 (57.7) |
18 (23.1) |
36 (46.2) |
57 (73.1) |
54 (69.2) |
II |
169 (50.6) |
78 (46.2) |
83 (49.1) |
36 (21.3) |
67 (39.6) |
126 (74.6) |
89 (52.7) |
III |
81 (24.3) |
48 (59.3) |
49 (60.5) |
19 (23.5) |
33 (40.7) |
63 (77.8) |
45 (55.6) |
IV |
6 (1.8) |
6 (100.0) |
6 (100.0) |
2 (33.3) |
5 (83.3) |
6 (100.0) |
3 (50.0) |
p-value |
|
0.007*
|
0.037*
|
0.896 |
0.159 |
0.475 |
0.100 |
Nuclear grade |
|
|
|
|
|
|
|
1 |
39 (11.7) |
20 (51.3) |
23 (59.0) |
4 (10.3) |
15 (38.5) |
34 (87.2) |
18 (46.2) |
2 |
168 (50.3) |
79 (47.0) |
90 (53.6) |
31 (18.5) |
68 (40.5) |
128 (76.2) |
89 (53.0) |
3 |
127 (38.0) |
65 (51.2) |
70 (55.1) |
40 (31.5) |
58 (45.7) |
90 (70.9) |
84 (66.1) |
p-value |
|
0.747 |
0.826 |
0.004*
|
0.590 |
0.112 |
0.026*
|
Histologic grade |
|
|
|
|
|
|
|
1 |
75 (22.5) |
34 (45.3) |
40 (53.3) |
9 (12.0) |
35 (46.7) |
61 (81.3) |
42 (56.0) |
2 |
136 (40.7) |
64 (47.1) |
73 (53.7) |
28 (20.6) |
61 (44.9) |
105 (77.2) |
81 (59.6) |
3 |
123 (36.8) |
66 (53.7) |
70 (56.9) |
38 (30.9) |
45 (36.6) |
86 (69.9) |
68 (55.3) |
p-value |
|
0.433 |
0.837 |
0.007*
|
0.273 |
0.160 |
0.764 |
ER |
|
|
|
|
|
|
|
– |
154 (46.1) |
79 (51.3) |
67 (43.5) |
48 (31.2) |
53 (34.4) |
102 (66.2) |
75 (48.7) |
+ |
180 (53.9) |
85 (47.2) |
116 (64.4) |
27 (15.0) |
88 (48.9) |
150 (83.3) |
116 (64.4) |
p-value |
|
0.458 |
0.000*
|
0.000*
|
0.008*
|
0.000*
|
0.004*
|
PR |
|
|
|
|
|
|
|
– |
184 (55.1) |
95 (51.6) |
97 (52.7) |
54 (29.3) |
68 (37.0) |
139 (75.5) |
92 (50.0) |
+ |
150 (44.9) |
69 (46.0) |
86 (57.3) |
21 (14.0) |
73 (48.7) |
113 (75.3) |
99 (66.0) |
p-value |
|
0.306 |
0.399 |
0.001*
|
0.031*
|
0.965 |
0.003*
|
HER2 |
|
|
|
|
|
|
|
– |
251 (75.1) |
108 (43.0) |
144 (57.4) |
52 (20.7) |
107 (42.6) |
193 (76.9) |
144 (57.4) |
+ |
83 (24.9) |
56 (67.5) |
39 (47.0) |
23 (27.7) |
34 (41.0) |
59 (71.1) |
47 (56.6) |
p-value |
|
0.000*
|
0.099 |
0.186 |
0.790 |
0.287 |
0.905 |
Table 2.Relationship between hedgehog related protein expression and breast cancer phenotype
|
Total (n = 290)a
|
LumA (n = 67) |
LumB HER2 neg (n = 43) |
LumB HER2 pos (n = 25) |
HER2 (n = 58) |
Triple negative (n = 97) |
p-value |
Shh |
|
|
|
|
|
|
|
– |
147 (50.7) |
33 (49.3) |
27 (62.8) |
12 (48.0) |
15 (25.9) |
60 (61.9) |
0.000*
|
+ |
143 (49.3) |
34 (50.7) |
16 (37.2) |
13 (52.0) |
43 (74.1) |
37 (38.1) |
|
Ptch |
|
|
|
|
|
|
|
– |
132 (45.5) |
21 (31.3) |
10 (23.3) |
13 (52.0) |
31 (53.4) |
57 (58.8) |
0.000*
|
+ |
158 (54.5) |
46 (68.7) |
33 (76.7) |
12 (48.0) |
27 (46.6) |
40 (41.2) |
|
Smo |
|
|
|
|
|
|
|
– |
225 (77.6) |
58 (86.6) |
40 (93.0) |
20 (80.0) |
40 (69.0) |
67 (69.1) |
0.004*
|
+ |
65 (22.4) |
9 (13.4) |
3 (7.0) |
5 (20.0) |
18 (31.0) |
30 (30.9) |
|
Gli-1 |
|
|
|
|
|
|
|
– |
171 (59.0) |
35 (52.2) |
25 (58.1) |
9 (36.0) |
40 (69.0) |
62 (63.9) |
0.039*
|
+ |
119 (41.0) |
32 (47.8) |
18 (41.9) |
16 (64.0) |
18 (31.0) |
35 (36.1) |
|
Gli-2 |
|
|
|
|
|
|
|
– |
75 (25.9) |
10 (14.9) |
8 (18.6) |
5 (20.0) |
20 (34.5) |
32 (33.0) |
0.031*
|
+ |
215 (74.1) |
57 (85.1) |
35 (81.4) |
20 (80.0) |
38 (65.5) |
65 (67.0) |
|
Gli-3 |
|
|
|
|
|
|
|
– |
122 (42.1) |
17 (25.4) |
20 (46.5) |
6 (24.0) |
30 (51.7) |
49 (50.5) |
0.003*
|
+ |
168 (57.9) |
50 (74.6) |
23 (53.5) |
19 (76.0) |
28 (48.3) |
48 (49.5) |
|
Table 3.Kaplan-Meier analysis of the overall survival rates
|
|
Breast carcinoma (n = 322)
|
|
|
Total |
No. of deceased |
p-value |
Age (yr) |
< 50 |
170 |
17 |
0.233 |
|
≥ 50 |
152 |
19 |
|
Stage |
I |
73 |
2 |
0.000*
|
|
II |
163 |
14 |
|
|
III |
80 |
16 |
|
|
IV |
6 |
4 |
|
Phenotype |
LumA |
67 |
1 |
0.130 |
|
LumB HER2 neg |
43 |
8 |
|
|
LumB HER2 pos |
25 |
1 |
|
|
HER2 |
58 |
5 |
|
|
Triple negative |
97 |
9 |
|
Shh |
– |
167 |
17 |
0.447 |
|
+ |
155 |
19 |
|
Ptch |
– |
147 |
15 |
0.638 |
|
+ |
175 |
21 |
|
Smo |
– |
252 |
27 |
0.695 |
|
+ |
70 |
9 |
|
Gli-1 |
– |
186 |
25 |
0.354 |
|
+ |
136 |
11 |
|
Gli-2 |
– |
79 |
2 |
0.012*
|
|
+ |
243 |
34 |
|
Gli-3 |
– |
139 |
21 |
0.469 |
|
+ |
183 |
15 |
|