Clinicopathologic Characteristics of Breast Cancer According to the Infiltrating Immune Cell Subtypes
Abstract
:1. Introduction
2. Results
2.1. Basal Characteristics of Breast Cancer Patients
2.2. Expression of Immune Cell Subtype-Related Proteins According to the Breast Cancer Molecular Subtype
2.3. Correlations among the Expression Statuses of Immune Cell Subtype-Related Proteins
2.4. Correlation between Clinicopathologic Parameters and the Expression Statuses of Immune Cell Subtype-Related Proteins
2.5. Impact of Immune Cell Subtype-Related Protein Expression on Patient Prognosis
3. Discussion
4. Materials and Methods
4.1. Patient Selection and Histologic Evaluation
4.2. Tissue Microarray
4.3. Immunohistochemistry
4.4. Immunohistochemistry Interpretation
4.5. Breast Cancer Molecular Classification
4.6. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Parameter | Total (n = 334) (%) | Luminal A (n = 162) (%) | Luminal B (n = 96) (%) | HER-2 (n = 21) (%) | TNBC (n = 55) (%) | p-Value |
---|---|---|---|---|---|---|
STAT4 | 0.809 | |||||
Low | 237 (71.0) | 115 (71.0) | 71 (74.0) | 14 (66.7) | 37 (67.3) | |
High | 97 (29.0) | 47 (29.0) | 25 (26.0) | 7 (33.3) | 18 (32.7) | |
STAT6 | 0.047 | |||||
Low | 252 (75.4) | 131 (80.9) | 65 (67.7) | 13 (61.9) | 43 (78.2) | |
High | 82 (24.6) | 31 (19.1) | 31 (32.3) | 8 (38.1) | 12 (21.8) | |
FOXP3 | 0.006 | |||||
Low | 300 (89.8) | 151 (93.2) | 88 (91.7) | 15 (71.4) | 46 (83.6) | |
High | 34 (10.2) | 11 (6.8) | 8 (8.3) | 6 (28.6) | 9 (16.4) | |
CD8 | <0.001 | |||||
Low | 292 (87.4) | 155 (95.7) | 78 (81.3) | 12 (57.1) | 47 (85.5) | |
High | 42 (12.6) | 7 (4.3) | 18 (18.8) | 9 (42.9) | 8 (14.5) | |
CD68 | 0.026 | |||||
Low | 183 (54.8) | 101 (62.3) | 48 (50.0) | 7 (33.3) | 27 (49.1) | |
High | 151 (45.2) | 61 (37.7) | 48 (50.0) | 14 (66.7) | 28 (50.9) | |
CD163 | <0.001 | |||||
Low | 223 (66.8) | 131 (80.9) | 57 (59.4) | 8 (38.1) | 27 (49.1) | |
High | 111 (33.2) | 31 (19.1) | 39 (40.6) | 13 (61.9) | 28 (50.9) |
Parameter | Total (n = 334) (Mean ± SD) | Luminal A (n = 162) (Mean ± SD) | Luminal B (n = 96) (Mean ± SD) | HER-2 (n = 21) (Mean ± SD) | TNBC (n = 55) (Mean ± SD) | p-Value |
---|---|---|---|---|---|---|
STAT4 H-score | 87.7 ± 56.6 | 87.8 ± 53.6 | 81.8 ± 55.3 | 102.8 ± 65.0 | 92.0 ± 64.0 | 0.417 |
STAT6 H-score | 2.6 ± 7.3 | 1.5 ± 3.9 | 3.5 ± 8.1 | 7.1 ± 16.3 | 2.7 ± 7.9 | 0.005 |
FOXP3 (%) | 0.5 ± 1.5 | 0.3 ± 1.2 | 0.4 ± 1.3 | 1.6 ± 2.8 | 0.8 ± 1.8 | 0.001 |
CD8 (%) | 6.3 ± 7.9 | 5.2 ± 5.3 | 7.6 ± 9.6 | 10.2 ± 8.1 | 6.1 ± 10.1 | 0.012 |
CD68 (%) | 1.0 ± 1.9 | 0.7 ± 1.6 | 1.0 ± 1.7 | 1.4 ± 2.4 | 1.7 ± 2.7 | 0.011 |
CD163 (%) | 14.6 ± 15.6 | 9.7 ± 11.7 | 17.4 ± 17.1 | 22.1 ± 17.4 | 21.4 ± 17.9 | <0.001 |
Parameter | Total breast cancer | Luminal A | Luminal B | HER-2 | TNBC | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
No LPBC n = 292 (%) |
LPBC n = 42 (%) | p-Value |
No LPBC n = 154 (%) |
LPBC n = 8 (%) | p-Value |
No LPBC n = 81 (%) |
LPBC n = 15 (%) | p-Value |
No LPBC n = 13 (%) |
LPBC n = 8 (%) | p-Value |
No LPBC n = 44 (%) |
LPBC n = 11 (%) | p-Value | |
STAT4 | <0.001 | 0.171 | 0.060 | 0.041 | 0.021 | ||||||||||
Low | 218 (74.7) | 19 (45.2) | 111 (72.1) | 4 (50.0) | 63 (77.8) | 8 (53.3) | 11 (84.6) | 3 (37.5) | 33 (75.0) | 4 (36.4) | |||||
High | 74 (25.3) | 23 (54.8) | 43 (27.9) | 4 (50.0) | 18 (22.2) | 7 (46.7) | 2 (15.4) | 5 (62.5) | 11 (25.0) | 7 (63.6) | |||||
STAT6 | <0.001 | 0.180 | 0.016 | 0.310 | 0.182 | ||||||||||
Low | 228 (78.1) | 24 (57.1) | 126 (81.8) | 5 (62.5) | 59 (72.8) | 6 (40.0) | 7 (53.8) | 6 (75.0) | 36 (81.8) | 7 (63.6) | |||||
High | 64 (21.9) | 18 (42.9) | 28 (18.2) | 3 (37.5) | 22 (27.2) | 9 (60.0) | 6 (46.2) | 2 (25.0) | 8 (18.2) | 4 (36.4) | |||||
FOXP3 | 0.010 | 0.510 | 0.107 | 0.410 | 0.582 | ||||||||||
Low | 267 (91.4) | 33 (78.6) | 144 (93.5) | 7 (87.5) | 76 (93.8) | 12 (80.0) | 10 (76.9) | 5 (62.5) | 37 (84.1) | 9 (81.8) | |||||
High | 25 (8.6) | 9 (21.4) | 10 (6.5) | 1 (12.5) | 5 (6.2) | 3 (20.0) | 3 (23.1) | 3 (37.5) | 7 (15.9) | 2 (18.2) | |||||
CD8 | <0.001 | <0.001 | <0.001 | 0.002 | 0.005 | ||||||||||
Low | 279 (95.5) | 13 (31.0) | 152 (98.7) | 3 (37.5) | 75 (92.6) | 3 (20.0) | 11 (84.6) | 1 (12.5) | 41 (93.2) | 6 (54.5) | |||||
High | 13 (4.5) | 29 (69.0) | 2 (1.3) | 5 (62.5) | 6 (7.4) | 12 (80.0) | 2 (15.4) | 7 (87.5) | 3 (6.8) | 5 (45.5) | |||||
CD68 | <0.001 | 0.003 | 0.002 | 0.112 | 0.023 | ||||||||||
Low | 177 (60.6) | 6 (14.3) | 100 (64.9) | 1 (12.5) | 46 (56.8) | 2 (13.3) | 6 (46.2) | 1 (12.5) | 25 (56.8) | 2 (18.2) | |||||
High | 115 (39.4) | 36 (85.7) | 54 (35.1) | 7 (87.5) | 35 (43.2) | 13 (86.7) | 7 (53.8) | 7 (87.5) | 19 (43.2) | 9 (81.8) | |||||
CD163 | <0.001 | <0.001 | 0.001 | 0.310 | 0.023 | ||||||||||
Low | 215 (73.6) | 8 (19.0) | 130 (84.4) | 1 (12.5) | 54 (66.7) | 3 (20.0) | 6 (46.2) | 2 (25.0) | 25 (56.8) | 2 (18.2) | |||||
High | 77 (26.4) | 34 (81.0) | 24 (15.6) | 7 (87.5) | 27 (33.3) | 12 (80.0) | 7 (53.8) | 6 (75.0) | 19 (43.2) | 9 (81.8) |
Parameters | STAT4 H-Score | STAT6 H-Score | FOXP3 | CD8 | CD68 | CD163 |
---|---|---|---|---|---|---|
ER | ||||||
r-coefficient | −0.086 | −0.148 | −0.197 | −0.046 | −0.131 | −0.298 |
p-value | 0.117 | 0.007 | <0.001 | 0.399 | 0.017 | <0.001 |
PR | ||||||
r-coefficient | −0.051 | −0.083 | −0.156 | −0.105 | −0.149 | −0.204 |
p-value | 0.357 | 0.131 | 0.004 | 0.055 | 0.006 | <0.001 |
Stromal TIL | ||||||
r-coefficient | 0.313 | 0.316 | 0.175 | 0.665 | 0.465 | 0.525 |
p-value | <0.001 | <0.001 | 0.001 | <0.001 | <0.001 | <0.001 |
Parameter | Number of Patients /Recurrence/Death | Disease-Free Survival | Overall Survival | ||
---|---|---|---|---|---|
Mean Survival (95% CI) Months | p-Value | Mean Survival (95% CI) Months | p-Value | ||
STAT4 | 0.346 | 0.074 | |||
Low | 237/23/17 | 101 (98–104) | 103 (101–105) | ||
High | 97/13/13 | 98 (93–103) | 100 (97–104) | ||
STAT6 | 0.995 | 0.054 | |||
Low | 252/27/27 | 100 (97–103) | 102 (99–104) | ||
High | 82/9/3 | 100 (95–105) | 105 (102–108) | ||
FOXP3 | 0.672 | 0.957 | |||
Low | 300/33/27 | 100 (97–102) | 102 (100–104) | ||
High | 34/3/3 | 101 (94–108) | 103 (99–108) | ||
CD8 | 0.003 | 0.475 | |||
Low | 292/26/25 | 101 (99–104) | 103 (101–105) | ||
High | 42/10/5 | 90 (81–99) | 99 (94–105) | ||
CD68 | 0.136 | 0.629 | |||
Low | 183/15/15 | 100 (97–103) | 101 (99–104) | ||
High | 151/21/15 | 99 (95–102) | 103 (100–105) | ||
CD163 | 0.714 | 0.681 | |||
Low | 223/23/19 | 100 (97–103) | 103 (101–105) | ||
High | 111/13/11 | 100 (95–104) | 102 (99–105) |
Parameters | Disease-Free Survival | Overall Survival | ||||
---|---|---|---|---|---|---|
Hazard Ratio | 95% CI | p-Value | Hazard Ratio | 95% CI | p-Value | |
Age | 0.627 | 0.021 | ||||
≤50 versus >50 | 1.185 | 0.597–2.353 | 2.418 | 1.145–5.108 | ||
Histologic grade | 0.220 | 0.201 | ||||
I/II versus III | 1.674 | 0.735–3.814 | 1.784 | 0.734–4.338 | ||
T stage | 0.765 | 0.816 | ||||
T1 versus T2/3 | 0.900 | 0.451–1.797 | 0.915 | 0.436–1.923 | ||
Lymph node metastasis | 0.022 | 0.163 | ||||
No versus Yes | 2.247 | 1.125–4.488 | 1.708 | 0.805–3.626 | ||
ER status | 0.162 | 0.453 | ||||
Negative versus Positive | 0.481 | 0.173–1.342 | 1.490 | 0.526–4.218 | ||
PR status | 0.893 | 0.840 | ||||
Negative versus Positive | 0.943 | 0.404–2.203 | 1.096 | 0.452–2.656 | ||
HER-2 status | 0.216 | 0.450 | ||||
Negative versus Positive | 1.628 | 0.752–3.525 | 1.400 | 0.585–3.348 | ||
Ki-67 L.I. | 0.539 | 0.489 | ||||
≤14 versus >14 | 1.258 | 0.542–2.917 | 0.705 | 0.262–1.897 | ||
CD8 | 0.026 | 0.975 | ||||
Low versus High | 2.435 | 1.110–5.344 | 0.984 | 0.355–2.728 |
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Kim, H.M.; Koo, J.S. Clinicopathologic Characteristics of Breast Cancer According to the Infiltrating Immune Cell Subtypes. Int. J. Mol. Sci. 2020, 21, 4438. https://doi.org/10.3390/ijms21124438
Kim HM, Koo JS. Clinicopathologic Characteristics of Breast Cancer According to the Infiltrating Immune Cell Subtypes. International Journal of Molecular Sciences. 2020; 21(12):4438. https://doi.org/10.3390/ijms21124438
Chicago/Turabian StyleKim, Hye Min, and Ja Seung Koo. 2020. "Clinicopathologic Characteristics of Breast Cancer According to the Infiltrating Immune Cell Subtypes" International Journal of Molecular Sciences 21, no. 12: 4438. https://doi.org/10.3390/ijms21124438