Background
Publication by | Laboratory Methodology | Cohort Characteristics | Prognostic Implications |
---|---|---|---|
Takada et al. [91] | IHC (RTJ2) | met-HER2+ BCA (n = 29), TPD | ↓ Low HER3 expression was associated with shortened PFS |
Adamczyk et al. [25] | IHC (SP71) | HER2+ BCA (n = 97), Adj.T | ↑ High HER3 expression (only with concurrent PTEN negativity) was associated with shorten MFS |
Duchnowska et al. [44] | VeraTag assay | HER2+ BCA (n = 189), Adj.T | - No correlation between HER3 expression and OS in advanced stage HER2 + BCA |
Nishimura et al. [54] | VeraTag assay | met-HER2+ BCA (n = 47), T | - HER3 expression did not has any influence on PFS in trastuzumab-refractory advanced HER2 + BCA |
Koutras et al. [39] | qRT-PCR | BCA (n = 663, HER2 + BCA n = 143) | ↓ Low HER3 mRNA (only with concurrently high EGFR, high HER2, low HER4 mRNA) was associated with worse DFS |
Baselga et al. [38] | qRT-PCR*, IHC** (DAK-H3-IC) | HER2+ BCA (n = 740*/497**), Adj.T | ↓ High HER3 mRNA was associated with better prognosis in metastatic HER2 + BCA |
Berghoff et al. [16] | IHC (DAK-H3-IC) | met-BCA (n = 110, met-HER2 + BCA n = 34) | ↑ High HER3 expression was associated with shorter OS in initially metastatic HER2 + BCA subgroup |
Park et al. [31] | IHC (DAK-H3-IC) | met-HER2+ BCA (n = 125), T | ↑ High HER3 expression was associated with worse PFS in initially metastatic HER2 + BCA |
Bae et al. [26] | IHC (DAK-H3-IC) | HR-BCA (n = 886, HER2 + BCA n = 221) | ↑ High HER3 expression was associated with poorer DFS in HER2 + BCA subgroup and poorer DFS and OS in TNBC |
Czopek et al. [48] | IHC (DAK-H3-IC) | HER2+ BCA (n = 35) | - No correlation between HER3 expression and DFS or OS |
Lipton et al. [29] | VeraTag assay | met-HER2+ BCA (n = 89), T | ↑ High HER3 expression was associated with shorter PFS in initially metastatic HER2 + BCA |
Gori et al. [41] | IHC (RTJ1) | met-HER2+ BCA (n = 61), T | - HER3 was not significantly associated with clinical outcome in initially metastatic HER2 + BCA |
Han et al. [37] | VeraTag assay | met-HER2+ BCA (n = 50), T | ↓ High HER3 expression was related to longer TTP in advanced HER2 + BCA |
Larsen et al. [43] | IHC (DAK-H3-IC) | ER+ BCA (n = 1062) | - HER3 expression did not shown any association to DFS |
Chiu et al. [27] | IHC (Ab-10 pAb) | BCA (n = 3123) | ↑ High HER3 expression was associated with decreased BCSS |
Yonemori et al. [45] | IHC (DAK-H3-IC) | HER2+ BCA (n = 44), neoAdj.T | - HER3 expression did not significantly correlate with pCR |
Giltnane et al. [28] | AQUA | BCA (n = 550) | ↑ High HER3 expression was associated with decreased survival |
Haas et al. [42] | IHC (SGP1) | HER2- BCA (n = 171) | - No prognostic value for HER3 |
Sassen et al. [50] | IHC (5A12), FISH | BCA (n = 173) | - No prognostic value for HER3 expression, HER3 gene amplification was related to decreased DFS |
Giuliani et al. [52] | IHC (RTJ1) | met-HER2+ BCA (n = 103), T | - No prognostic value for HER3 |
Lee et al. [36] | IHC (pAb) | BCA (n = 378) | ↓ High HER3 expression correlated with longer DFS |
Bianchi et al. [53] | IHC (RTJ1) | BCA (n = 145) | - No prognostic value for HER3 expression singly, but high co-expression of HER2/3/4 predicted worse prognosis |
Fuchs et al. [34] | IHC (C-17 pAb) | BCA (n = 48) | ↑ High HER3 expression singly and in co-expression with high HER1 and HER2 was associated with poor prognosis |
Robinson et al. [32] | IHC (polyclonal) | met-HER2+ BCA (n = 104), T | ↑ High HER3 expression was associated with worse OS |
Wiseman et al. [33] | IHC (2-18C9) | BCA (n = 242) | ↑ High HER3 expression independently and with high HER1 and/or HER2 was associated with decreased DSS |
Abd El-Rehim et al. [15] | IHC (RTJ1) | BCA (n = 1499) | - No prognostic value for HER3 singly, but in co-expression with high HER2 predicted unfavorable DFS and OS |
Smith et al. [49] | IHC | met-HER2+ BCA (n = 77), T | - No prognostic value for HER3 |
Bièche et al. [35] | qRT-PCR | BCA (n = 130) | ↑ High HER3 mRNA was associated with shorten RFS |
Witton et al. [30] | IHC (H3.105.5) | BCA (n = 220) | ↑ High HER3 expression was associated with reduced BCSS survival |
Suo et al. [47] | IHC (sc-415), RT-PCR | BCA (n = 100) | - High HER3 expression was predictive for reduced DFS or BCSS only in co-overexpression with HER2 or HER1 + HER2 |
Pawlowski et al. [40] | qRT-PCR | BCA (n = 365) | ↓ Elevated HER3 mRNA expression was associated with a better prognosis in terms of OS, but did not relate to RFS |
Travis et al. [46] | IHC (RTJ1) | BCA (n = 346), met-BCA (n = 145) | - No prognostic value for HER3 expression neither in primary nor metastatic breast cancer |
Lemoine et al. [51] | IHC (49.3 pAb) | BCA (n = 195) | - No demonstrable relationship between HER3 expression and survival |
Methods
Clinical sample material
Characteristic |
n
| BCA cohort, n (%) |
n
| HER2-amplified BCA cohort, n (%) |
---|---|---|---|---|
Follow-up period for RFS (range) |
Mean 10.4 yr. (1 mo.-22 yr.)
|
Mean 5.3 yr. (1 mo.-9 yr.)
| ||
Age (range) | 308 |
Median 61 yr. (32–93 yr.)
| 177 |
Median 60 yr. (29–91 yr.)
|
< 50 years | 64 (20.8) | 36 (20.3) | ||
≥ 50 years | 244 (79.2) | 141 (79.7) | ||
HER2 status | 308 | 177 | ||
Positive | 47 (15.3) | 177 (100.0) | ||
Negative | 261 (84.7) | 0 (0.0) | ||
ER status | 307 | 177 | ||
Positive (≥10%) | 248 (80.8) | 113 (63.8) | ||
Negative (< 10%) | 59 (19.2) | 64 (36.2) | ||
PR status | 307 | 177 | ||
Positive (≥10%) | 201 (65.5) | 74 (41.8) | ||
Negative (< 10%) | 106 (34.5) | 103 (58.2) | ||
Triple negativity | 307 | 177 | ||
TNBC (HER2−/ER-/PR-) | 30 (9.8) | 0 (0.0) | ||
No TNBC | 277 (90.2) | 177 (100.0) | ||
Histological grade | 232 | 174 | ||
I-II | 179 (77.2) | 41 (23.6) | ||
III | 53 (22.8) | 133 (76.4) | ||
Ki67 proliferation index | 230 | 177 | ||
Low (< 20%) | 165 (71.7) | 33 (18.6) | ||
High (≥20%) | 65 (28.3) | 144 (81.4) | ||
Histological type | 304 | 168 | ||
Ductal | 173 (56.9) | 156 (92.9) | ||
Lobular | 131 (43.1) | 12 (7.1) | ||
Tumour size | 177 | 142 | ||
< 2 cm | 57 (32.2) | 68 (47.9) | ||
≥ 2 cm | 120 (67.8) | 74 (52.1) | ||
Tumour size | 308 | 172 | ||
pT1-pT2 | 282 (91.6) | 161 (93.6) | ||
pT3-pT4 | 26 (8.4) | 11 (6.4) | ||
Lymph nodal spread | 286 | 169 | ||
Positive pN+ | 114 (39.9) | 73 (43.2) | ||
Negative pN0 | 172 (60.1) | 96 (56.8) |
Primary treatment | BCA cohort (n = 308) | HER2-amplified BCA cohort (n = 177) | ||
---|---|---|---|---|
n
|
%
|
n
|
%
| |
Breast surgery | ||||
Mastectomy (ablation) | 161 | 52.4 | 101 | 57.1 |
Conservative surgery (resection) | 146 | 47.6 | 72 | 40.7 |
No operation | 3 | 0.6 | ||
Unknown | 1 | |||
Post-operative radiotherapy | 198 | 65.3 | 110 | 62.1 |
No | 105 | 34.7 | 67 | 37.9 |
Unknown | 5 | |||
Adjuvant endocrine therapy | 97 | 32.1 | 104 | 58.8 |
No | 205 | 67.9 | 73 | 41.2 |
Unknown | 6 | |||
Adjuvant chemotherapy | 40 | 13.4 | 133 | 75.1 |
No | 259 | 86.6 | 44 | 24.9 |
Unknown | 9 | |||
Adjuvant trastuzumab | 82 | 46.3 | ||
No | 308 | 100.0 | 95 | 53.7 |
Immunohistochemical stainings
Antibody | Host species | Catalog No. | Clonality | Dilution | Manufacturer/distributor |
---|---|---|---|---|---|
Anti-Human HER3 | Mouse | M7297 | DAK-H3-IC | 1:100 | DAKO A/S, Glostrup, Denmark |
FLRF/RNF41 Antibody | Rabbit | A300-049A | polyclonal | 1:3000 | Bethyl Laboratories, Inc., Montgomery, Texas, USA |
Anti-Nedd4, WW2 domain | Rabbit | #07–049 | polyclonal | 1:750 | Merck KGaA, Darmstadt, Germany |
Cytokeratin 5 Antibody | Mouse | NCL-L-CK5 | XM26 | 1:150 | Leica Biosystems Newcastle Ltd., Newcastle Upon Tyne, UK |
Cytokeratin 14 Antibody | Mouse | NCL-L-LL0022 | LL0022 | 1:150 | Leica Biosystems, Newcastle Ltd., Newcastle Upon Tyne, UK |
Anti-human Ki67 | Mouse | BSH-7302 | BS4 | 1:100 | Nordic BioSite AB, Täby, Sweden |
Microscopic analysis and interpretation of immunoreactivity
Statistical analysis
Results
HER3 protein expression in breast carcinomas
HER3, NEDD4–1, and NRDP1 protein expression in HER2-amplified breast carcinomas
Association of HER3, NEDD4–1 and NRDP1 with clinicopathological characteristics
Characteristic |
BCA cohort HER2-amplified BCA cohort
| |||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
HER3-m (%) |
p
| HER3-c (%) |
p
| HER3-t (%) |
p
| HER3-m (%) |
p
| HER3-c (%) |
p
| HER3-t (%) |
p
| |||||||
- | + | - | + | - | + | - | + | - | + | - | + | |||||||
HER2 status | 0.615 | 0.990 | 0.882 | |||||||||||||||
Negative | 85.8 | 83.8 | 84.6 | 84.7 | 84.2 | 84.9 | ||||||||||||
Positive | 14.2 | 16.2 | 15.4 | 15.3 | 15.8 | 15.1 | ||||||||||||
Estrogen receptor status | 0.057 | 0.280 | 0.839 |
0.013*
| 0.376 | 0.104 | ||||||||||||
Negative | 23.6 | 15.1 | 30.8 | 18.7 | 18.4 | 19.5 | 54.3 | 31.7 | 46.7 | 35.2 | 46.5 | 32.8 | ||||||
Positive | 76.4 | 84.9 | 69.2 | 81.3 | 81.6 | 80.5 | 45.7 | 68.3 | 53.3 | 64.8 | 53.5 | 67.2 | ||||||
Progesterone receptor status |
0.002**
| 0.368 | 0.443 | 0.888 | 0.882 | 0.716 | ||||||||||||
Negative | 43.2 | 26.4 | 46.2 | 34.0 | 38.2 | 33.3 | 57.1 | 58.5 | 60.0 | 58.0 | 55.8 | 59.0 | ||||||
Positive | 56.8 | 73.6 | 53.8 | 66.0 | 61.8 | 66.7 | 42.9 | 41.5 | 40.0 | 42.0 | 44.2 | 41.0 | ||||||
Triple-negativity (HER2-/ER-/PR-) |
0.000***
| 0.099 | 0.798 | |||||||||||||||
No | 83.8 | 96.2 | 76.9 | 90.8 | 89.5 | 90.5 | ||||||||||||
Yes | 16.2 | 3.8 | 23.1 | 9.2 | 10.5 | 9.5 | ||||||||||||
Histological grade | 0.121 | 0.855 | 0.705 | 0.435 | 0.767 | 0.956 | ||||||||||||
I-II | 72.8 | 81.4 | 75.0 | 77.3 | 75.4 | 77.8 | 28.6 | 22.3 | 26.7 | 23.3 | 23.3 | 23.6 | ||||||
III | 27.2 | 18.6 | 25.0 | 22.7 | 24.6 | 22.2 | 71.4 | 77.7 | 73.3 | 76.7 | 76.7 | 76.4 | ||||||
Ki-67 proliferation index | 0.597 | 0.985 | 0.852 | 0.475 | 0.213 | 0.658 | ||||||||||||
Low | 73.4 | 70.2 | 71.4 | 71.7 | 72.7 | 71.4 | 22.9 | 17.6 | 6.7 | 19.8 | 20.9 | 17.9 | ||||||
High | 26.6 | 29.8 | 28.6 | 28.3 | 27.3 | 28.6 | 77.1 | 82.4 | 93.3 | 80.2 | 79.1 | 82.1 | ||||||
Histological type | 0.629 | 0.359 | 0.204 | 0.055 | 0.940 | 0.960 | ||||||||||||
Ductal | 55.5 | 58.2 | 69.2 | 56.4 | 63.2 | 54.8 | 85.3 | 94.8 | 93.3 | 92.8 | 92.7 | 92.9 | ||||||
Lobular | 44.5 | 41.8 | 30.8 | 43.6 | 36.8 | 45.2 | 14.7 | 5.2 | 6.7 | 7.2 | 7.3 | 7.1 | ||||||
Lymph nodal status | 0.531 | 0.637 | 0.716 | 0.232 | 0.169 |
0.035*
| ||||||||||||
Negative pN0 | 58.3 | 61.9 | 66.7 | 59.9 | 62.0 | 59.5 | 65.7 | 54.5 | 40.0 | 58.4 | 42.9 | 61.4 | ||||||
Positive pN+ | 41.7 | 38.1 | 33.3 | 40.1 | 38.0 | 40.5 | 34.3 | 45.5 | 60.0 | 41.6 | 57.1 | 38.6 | ||||||
Tumor size (TNM stage) | 0.840 | 0.921 | 0.781 | 0.173 |
0.001***
| 0.368 | ||||||||||||
pT1-pT2 | 91.9 | 91.3 | 92.3 | 91.5 | 90.8 | 91.8 | 88.6 | 94.9 | 73.3 | 95.5 | 90.7 | 94.6 | ||||||
pT3-pT4 | 8.1 | 8.7 | 7.7 | 8.5 | 9.2 | 8.2 | 11.4 | 5.1 | 26.7 | 4.5 | 9.3 | 5.4 | ||||||
Tumor size (cm) |
0.003**
| 0.834 | 0.357 | 0.643 |
0.014*
| 0.143 | ||||||||||||
<2cm | 21.6 | 42.7 | 28.6 | 32.4 | 26.7 | 34.1 | 51.7 | 46.9 | 15.4 | 51.2 | 37.1 | 51.4 | ||||||
≥2cm | 78.4 | 57.3 | 71.4 | 67.6 | 73.3 | 65.9 | 48.3 | 53.1 | 84.6 | 48.8 | 62.9 | 48.6 | ||||||
Patient age at diagnosis | 0.726 | 0.624 | 0.217 | 0.069 |
0.000***
| 0.156 | ||||||||||||
<50 years | 21.6 | 20.0 | 15.4 | 21.0 | 15.8 | 22.4 | 31.4 | 17.6 | 60.0 | 16.7 | 27.9 | 17.9 | ||||||
≥50 years | 78.4 | 80.0 | 84.6 | 79.0 | 84.2 | 77.6 | 68.6 | 82.4 | 40.0 | 83.3 | 72.1 | 82.1 | ||||||
Cytokeratin 5/14 expression | 0.583 | 0.561 | 0.006** | |||||||||||||||
Negative | 85.3 | 88.7 | 92.9 | 87.6 | 76.2 | 92.0 | ||||||||||||
Positive | 14.7 | 11.3 | 7.1 | 12.4 | 23.8 | 8.0 | ||||||||||||
Basal phenotype (CK5/14+, ER-) | 0.191 | 0.801 |
0.001***
| |||||||||||||||
No | 85.3 | 92.5 | 92.9 | 90.8 | 78.6 | 95.2 | ||||||||||||
Yes | 14.7 | 7.5 | 7.1 | 9.2 | 21.4 | 4.8 |
Characteristic | Cytoplasmic NRDP1 expression n (%) | Nuclear NRDP1 expression n (%) | Cellular NEDD4–1 expression n (%) | |||||||
---|---|---|---|---|---|---|---|---|---|---|
n
| NRDP1- | NRDP1+ |
p
| NRDP1- | NRDP1+ |
p
| NEDD4–1- | NEDD4–1+ |
p
| |
Cases | 145 | 133 (91.7) | 12 (8.3) | 133 (91.7) | 12 (8.3) | 25 (17.2) | 120 (82.8) | |||
Estrogen receptor | 0.057 | 0.206 | 0.421 | |||||||
Positive | 97 | 86 (64.7) | 11 (91.7) | 87 (65.4) | 10 (83.3) | 15 (60.0) | 82 (68.3) | |||
Negative | 48 | 47 (35.3) | 1 (8.3) | 46 (34.6) | 2 (16.7) | 10 (40.0) | 38 (31.7) | |||
Progesterone receptor |
0.006**
| 0.125 | 0.053 | |||||||
Positive | 66 | 56 (42.1) | 10 (83.3) | 58 (43.6) | 8 (66.7) | 7 (28.0) | 59 (49.2) | |||
Negative | 79 | 77 (57.9) | 2 (16.7) | 75 (56.4) | 4 (33.3) | 18 (72.0) | 61 (50.8) | |||
Histological grade | 0.953 | 0.446 | 0.134 | |||||||
I-II | 35 | 32 (24.2) | 3 (25.0) | 31 (23.5) | 4 (33.3) | 9 (36.0) | 26 (21.8) | |||
III | 109 | 100 (75.8) | 9 (75.0) | 101 (76.5) | 8 (66.7) | 16 (64.0) | 93 (78.2) | |||
Ki-67 proliferation index | 0.228 | 0.228 | 1.000 | |||||||
Low | 29 | 25 (18.8) | 4 (33.3) | 25 (18.8) | 4 (33.3) | 5 (25.0) | 24 (20.0) | |||
High | 116 | 108 (81.2) | 8 (66.7) | 108 (81.2) | 8 (66.7) | 20 (75.0) | 96 (80.0) | |||
Histological type |
0.022*
| 0.880 | 0.403 | |||||||
Ductal | 128 | 119 (93.7) | 9 (75.0) | 118 (92.2) | 10 (90.9) | 22 (88.0) | 106 (93.0) | |||
Lobular | 11 | 8 (6.3) | 3 (25.0) | 10 (7.8) | 1 (9.1) | 3 (12.0) | 8 (7.0) | |||
Lymph nodal status | 0.120 | 0.277 | 0.516 | |||||||
Positive pN+ | 60 | 58 (45.3) | 2 (20.0) | 53 (42.1) | 7 (58.3) | 9 (37.5) | 51 (44.7) | |||
Negative pN0 | 78 | 70 (54.7) | 8 (80.0) | 73 (57.9) | 5 (41.7) | 15 (62.5) | 63 (55.3) | |||
Tumor size (cm) | 0.669 | 0.820 | 0.715 | |||||||
< 2 cm | 57 | 52 (48.1) | 5 (55.6) | 52 (49.1) | 5 (45.5) | 9 (45.0) | 48 (49.5) | |||
≥ 2 cm | 60 | 56 (51.9) | 4 (44.4) | 54 (50.9) | 6 (54.5) | 11 (55.0) | 49 (50.5) | |||
Tumor size (TNM stage) | 0.511 | 0.341 | 0.177 | |||||||
pT1-pT2 | 138 | 127 (96.2) | 11 (100.0) | 127 (96.9) | 11 (91.7) | 23 (92.0) | 115 (97.5) | |||
pT3-pT4 | 5 | 5 (3.8) | 0 (0.0) | 4 (3.1) | 1 (8.3) | 2 (8.0) | 3 (2.5) | |||
Patient age at diagnosis | 0.856 |
0.004**
| 0.771 | |||||||
< 50 years | 27 | 25 (18.8) | 2 (16.7) | 21 (15.8) | 6 (50.0) | 4 (16.0) | 23 (19.2) | |||
≥ 50 years | 118 | 108 (81.2) | 10 (83.3) | 112 (84.2) | 6 (50.0) | 21 (84.0) | 97 (80.8) | |||
HER3 membrane expression | 0.905 | 0.505 |
0.002**
| |||||||
Low | 26 | 24 (18.0) | 2 (16.7) | 23 (17.3) | 3 (25.0) | 10 (40.0) | 16 (13.3) | |||
High | 119 | 109 (82.0) | 10 (83.3) | 110 (82.7) | 9 (75.0) | 15 (60.0) | 104 (86.7) | |||
HER3 cytoplasmic expression | 0.300 | 0.215 | 0.360 | |||||||
Low | 11 | 11 (8.3) | 0 (0.0) | 9 (6.8) | 2 (16.7) | 3 (12.0) | 8 (6.7) | |||
High | 134 | 122 (91.7) | 12 (100.0) | 124 (93.2) | 10 (83.3) | 22 (88.0) | 112 (93.3) | |||
HER3 total cellular expression |
0.041*
| 0.942 | 0.620 | |||||||
Low | 35 | 35 (26.3) | 0 (0.0) | 32 (24.1) | 3 (25.0) | 7 (28.0) | 28 (23.3) | |||
High | 110 | 98 (73.7) | 12 (100.0) | 101 (75.9) | 9 (75.0) | 18 (72.0) | 92 (76.7) | |||
Cytokeratin 5/14 expression | 0.199 | 0.199 | 0.578 | |||||||
Negative | 127 | 115 (87.8) | 12 (100.0) | 115 (87.8) | 12 (100.0) | 23 (92.0) | 104 (88.1) | |||
Positive | 16 | 16 (12.2) | 0 (0.0) | 16 (12.2) | 0 (0.0) | 2 (8.0) | 14 (11.9) |
Prognostic implications of HER3, NEDD4–1 and NRDP1 in breast cancer
Characteristic | Univariate analysis Multivariate analysis | ||||||
---|---|---|---|---|---|---|---|
n |
p
| Mean RFS | 95% CI for RFS |
p
| Exp (B) | 95% CI for Exp (B) | |
Estrogen receptor status | 177 | 0.090 | |||||
Progesterone receptor status | 177 | 0.176 | |||||
Histological grade | 174 | 0.831 | |||||
Ki-67 proliferation index | 177 | 0.171 | |||||
Histological type (lobular/ductal) | 168 | 0.774 | |||||
Lymph nodal status pN+ (vs pN0) | 169 | 0.000*** | 6.7 (8.4) | 5.9 (8.0) – 7.5 (8.7) | 0.002** | 3.486 | 1.608, 7.555 |
Tumor size TNM stage ≥ pT3 (vs < pT3) | 172 | 0.000*** | 4.2 (7.9) | 2.3 (7.5) – 6.2 (8.3) | 0.001*** | 4.016 | 1.703, 9.468 |
Patient age at diagnosis | 177 | 0.118 | |||||
Menopausal status | 176 | 0.082 | |||||
Cytokeratin 5/14 expression | 167 | 0.447 | |||||
Basal phenotype (CK5/14+, ER-) | 167 | 0.955 | |||||
Total cellular HER3 low (vs high) | 177 | 0.004** | 6.3 (8.0) | 5.3 (7.6) – 7.3 (8.4) | 0.020* | 2.305 | 1.143, 4.648 |
Membranous HER3 low (vs high) | 177 | 0.025* | 6.6 (7.9) | 5.6 (7.4) – 7.7 (8.3) | |||
Cytoplasmic HER3 low (vs high) | 177 | 0.010* | 5.9 (7.8) | 4.2 (7.4) – 7.6 (8.2) | |||
NEDD4–1 expression | 145 | 0.261 | |||||
NRDP1 nuclear expression | 145 | 0.689 | |||||
NRDP1 cytoplasmic expression | 145 | 0.711 |