Background
Materials and methods
Patients and data analysis
IHC
Indirect immunofluorescence
Western blotting
Results
Analysis of BCL3 expression in tamoxifen adapted cell lines (MCF-7-TamR)
Distribution of BCL3 abundance by immunohistochemistry in the patient cohort
Tumor type | number | BCL3-IRScyt lo/hi > 8 (high %) | Significance | number | BCL3-IRSnuc lo/hi > 8 (high %) | Significance |
---|---|---|---|---|---|---|
All | 180 | 123/57 (31.7%) | 180 | 139/41 (22.8%) | ||
Menopause | 0.839 | 0.657 | ||||
Pre- | 35 | 24/11 (31.4%) | 35 | 28/7 (20.0%) | ||
Post- | 127 | 89/38 (29.9%) | 127 | 95/32 (25.2%) | ||
ER | 0.063 | 0.826 | ||||
Negative | 35 | 20/15 (42.9%) | 35 | 26/9 (25.7%) | ||
Positive | 126 | 93/33 (26.2%) | 126 | 96/30 (23.8%) | ||
PR | 0.487 | 0.459 | ||||
Negative | 69 | 46/23 (24.0%) | 69 | 50/19 (27.5%) | ||
Positive | 92 | 67/25 (27.2%) | 92 | 72/20 (21.7%) | ||
HER2 | 0.836 | 0.181 | ||||
Negative | 123 | 88/35 (28.5%) | 123 | 97/26 (21.1%) | ||
Positive | 36 | 25/11 (30.6%) | 36 | 24/12 (33.3%) | ||
TNBC | 1.000 | 0.599 | ||||
No | 137 | 97/40 (29.2%) | 137 | 103/34 (24.8%) | ||
Yes | 22 | 16/6 (27.3%) | 22 | 18/4 (18.2%) | ||
Lymph node | 0.285 | 0.191 | ||||
Negative | 95 | 64/31 (32.6%) | 95 | 68/27 (28.4%) | ||
Positive | 64 | 49/15 (23.4%) | 64 | 52/12 (18.8%) | ||
Grading | 0.257 § | 0.190 § | ||||
1 | 19 | 13/6 (31.6%) | 19 | 16/3 (15.8%) | ||
2 | 92 | 69/23 (25.0%) | 92 | 71/21 (22.8%) | ||
3 | 50 | 31/19 (38.0%) | 50 | 35/15 (30.0%) | ||
Histology | 0.244 | 0.847 | ||||
Ductal | 129 | 91/38 (29.5%) | 129 | 98/31 (24.0%) | ||
Lobular | 23 | 19/4 (17.4%) | 23 | 18/5 (21.7%) | ||
Other | 6 | 3/3 (50.0%) | 6 | 4/2 (33.3%) | ||
T > 2 | 0.059 | 0.462 | ||||
No | 76 | 59/17 (22.4%) | 76 | 60/16 (21.1%) | ||
Yes | 85 | 54/31 (36.5%) | 85 | 62/23 (27.1%) | ||
Chemo-therapy | 0.604 | 0.712 | ||||
No | 79 | 54/25 (31.7%) | 97 | 59/20 (20.6%) | ||
Yes | 81 | 59/22 (27.2%) | 81 | 63/18 (22.2%) | ||
Radio-therapy | 0.586 | 0.432 | ||||
No | 52 | 35/17 (32.7%) | 52 | 37/15 (28.8%) | ||
Yes | 109 | 78/31 (28.4%) | 109 | 85/24 (22.0%) | ||
Endocrine therapy | 0.438 | 0.841 | ||||
None | 29 | 18/11 (37.9%) | 29 | 23/6 (20.7%) | ||
Tamoxifen | 86 | 64/22 (25.6%) | 86 | 65/21 (24.4%) | ||
Aromatase inhibitor | 45 | 31/14 (31.1%) | 45 | 33/12 (26.7%) | ||
Tam-relapse* | 0.001 | 0.001 | ||||
No | 55 | 49/6 (10.9%) | 55 | 49/6 (10.9%) | ||
Yes | 25 | 13/12 (48.0%) | 25 | 13/12 (48.0%) | ||
Ki-67 | 0.001 | 0.187 | ||||
0–1 | 102 | 80/22 (21.6%) | 102 | 82/20 (19.6%) | ||
2–3 | 64 | 34/30 (46.9%) | 64 | 45/19 (29.7%) |
Survival analysis
Cytoplasmic BCL3 | Nuclear BCL3 | |||||||
---|---|---|---|---|---|---|---|---|
> 8 | Mean survival | SEM | p | > 8 | Mean survival | SEM | p | |
All cases | Low | 118.6 | 6.0 | 0.046 | Low | 121.6 | 5.8 | 0.002 |
High | 70.7 | 7.7 | High | 59.0 | 7.2 | |||
Premenopausal | Low | 112.6 | 12.7 | 0.533 | Low | 115.5 | 11.8 | 0.196 |
High | 68.8 | 15.1 | High | 50.6 | 12.5 | |||
Postmenopausal | Low | 118.8 | 6.8 | 0.057 | Low | 122.0 | 6.5 | 0.006 |
High | 70.0 | 8.6 | High | 58.6 | 8.0 | |||
Ductal | Low | n.a. * | 0.353 | Low | n.a. * | 0.041 | ||
High | n.a. * | High | n.a. * | |||||
Lobular | Low | n.a. * | 0.001 | Low | n.a. * | 0.003 | ||
High | n.a. * | High | n.a. * | |||||
Other | Low | n.a. * | 0.564 | Low | n.a. * | 0.317 | ||
High | n.a. * | High | n.a. * | |||||
T < 2 | Low | 128.6 | 7.4 | 0.677 | Low | 132.8 | 7.1 | 0.087 |
High | 82.8 | 10.2 | High | 72.0 | 10.8 | |||
T > 2 | Low | 91.8 | 7.6 | 0.112 | Low | 94.2 | 7.1 | 0.025 |
High | 62.4 | 9.4 | High | 44.2 | 6.2 | |||
N0 | Low | 128.1 | 7.2 | .207 | Low | 133.3 | 6.6 | 0.006 |
High | 77.9 | 9.6 | High | 54.4 | 6.1 | |||
N1 | Low | 92.0 | 7.8 | 0.146 | Low | 93.7 | 7.6 | 0.046 |
High | 47.3 | 9.0 | High | 49.5 | 12.3 | |||
G1 | Low | 113.5 | 7.2 | 0.536 | Low | n.a. * | 0.552 | |
High | 57.3 | 5.0 | High | n.a. * | ||||
G2 | Low | 121.7 | 7.4 | 0.009 | Low | n.a. * | < 0.001 | |
High | 55.6 | 10.6 | High | n.a. * | ||||
G3 | Low | 82.9 | 10.3 | 0.975 | Low | n.a. * | 0.665 | |
High | 73.4 | 11.6 | High | n.a. * | ||||
ER-neg | Low | 78.8 | 12.7 | 0.454 | Low | 90.8 | 11.3 | 0.376 |
High | 84.8 | 13.0 | High | 42.4 | 7.6 | |||
ER-pos | Low | 123.8 | 6.3 | 0.005 | Low | 123.8 | 6.3 | 0.004 |
High | 60.5 | 8.4 | High | 60.4 | 8.2 | |||
PR-neg | Low | 93.5 | 8.2 | 0.740 | Low | 98.4 | 7.6 | 0.108 |
High | 75.7 | 10.3 | High | 55.8 | 10.3 | |||
PR-pos | Low | 124.6 | 7.4 | 0.017 | Low | 125.2 | 7.3 | 0.007 |
High | 64.5 | 9.6 | High | 50.1 | 7.4 | |||
HER2-neg | Low | 125.3 | 6.4 | 0.019 | Low | 126.8 | 6.1 | 0.002 |
High | 72.1 | 8.9 | High | 61.8 | 8.6 | |||
HER2-pos | Low | 74.9 | 10.3 | 0.683 | Low | 82.6 | 10.2 | 0.361 |
High | 57.0 | 9.0 | High | 45.0 | 7.8 | |||
No TNBC | Low | n.a. * | 0.024 | Low | 123.8 | 6.0 | 0.003 | |
High | n.a. * | High | 61.0 | 7.7 | ||||
TNBC | Low | n.a. * | 0.357 | Low | 92.6 | 14.3 | 0.280 | |
High | n.a. * | High | 43.3 | 14.5 | ||||
Radiotherapy no | Low | 108.7 | 7.5 | 0.107 | Low | 108.6 | 7.6 | 0.133 |
High | 67.5 | 12.3 | High | 56.0 | 8.7 | |||
Radiotherapy yes | Low | 114.2 | 7.7 | 0.180 | Low | 118.6 | 7.2 | 0.008 |
High | 69.1 | 9.4 | High | 55.8 | 8.7 | |||
Ki-67 < 2 | Low | 129.9 | 6.3 | 0.012 | Low | 133.5 | 5.9 | < 0.001 |
High | 59.6 | 10.6 | High | 49.5 | 6.9 | |||
Ki-67 ≥ 2 | Low | 70.2 | 10.6 | 0.747 | Low | 75.5 | 9.8 | 0.919 |
High | 70.6 | 11.0 | High | 59.8 | 11.1 | |||
Chemotherapy no | Low | 133.1 | 6.1 | 0.019 | Low | 131.5 | 6.2 | 0.03 |
High | 72.9 | 9.3 | High | 58.0 | 7.6 | |||
Chemotherapy yes | Low | 101.7 | 8.9 | 0.379 | Low | 107.6 | 8.7 | 0.028 |
High | 64.4 | 10.7 | High | 48.9 | 8.6 | |||
No endocrine therapy | Low | n.a. * | 0.171 | Low | 85.3 | 12.5 | 0.861 | |
High | n.a. * | High | 48.1 | 11.1 | ||||
Tamoxifen | Low | n.a. * n.a. *§ | < 0.001 < 0.001§ | Low | 121.4 124.7§ | 7.7 7.6§ | < 0.001 < 0.001§ | |
High | n.a. * n.a. *§ | High | 36.7 36.2§ | 6.3 | ||||
Aromatase Inhibitor | Low | n.a. * n.a. *§ | 0.108 0.122§ | Low | 111.0 108.8 | 8.1 9.0 | 0.53 0.463§ | |
High | n.a. * n.a. *§ | High | 95.7 95.7 | 6.0 6.0 |
Univariate cox regression | |||
---|---|---|---|
Parameter | HR | 95% CI | p |
BCL3 cyt. * | 1.853 5.095 | 1.002–3.428 2.281–11.381 | 0.049 < 0.001 |
BCL3 nucl. * | 2.483 5.379 | 1.350–4.566 2.411–12.003 | 0.003 < 0.001 |
ER | 0.654 | 0.396–1.081 | 0.098 |
HER2/NEU | 1.700 | 1.034–2.795 | 0.036 |
N | 1.841 | 1.174–2.887 | 0.008 |
Multivariate cox regression | |||
BCL3 cyt* | 1.790 5.669 | 0.945–3.390 2.520–12.754 | 0.074 < 0.001 |
HER2/Neu* | 1,716 2.867 | 0.902–3.268 1.272–6.462 | 0.100 0.011 |
N* | 1.918 1.977 | 1.044–3.522 0.886–4.409 | 0.036 0.096 |
Multivariate cox regression | |||
BCL3 nuc. * | 2.857 6,740 | 1.536–5.312 2.764–16.436 | 0.001 < 0.001 |
HER2/Neu* | 2.014 | 0.889–4.562 | > 0.2 0.093 |
N* | 1.988 2.849 | 1.083–3.648 1.210–6.707 | 0.026 0.017 |