Tumour-Infiltrating Inflammatory Cells in Early Breast Cancer: An Underrated Prognostic and Predictive Factor?
Abstract
:1. Introduction
2. Results
2.1. CD1a/CD20 Immunostaining
2.2. CD45RO/CD4 Immunostaining
2.3. Immunoscore
3. Discussion
3.1. CD1a+ Dendritic Cells
3.2. CD45RO+ Memory T Cells
3.3. CD20+ B Cells
3.4. CD4+ T-Helper Cells
3.5. Immunoscore
4. Materials and Methods
4.1. Breast Cancer Patients and Clinical Data
4.2. TMA Construction and Immunohistochemistry
4.3. Quantification of Inflammatory Cells
4.4. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
TIIC | Tumour-infiltrating inflammatory cell |
APBI | Accelerated partial breast irradiation |
TMA | Tissue microarray |
TAM | Tumour-associated macrophage |
CT | Central tumour |
IF | Invasive front |
prox | Normal tissue in tumour proximity |
dist | Normal tissue sampled distant from the tumour |
HR+/- | Hormone receptor positive/negative |
BC | Breast cancer |
RT | Radiotherapy |
ER | Oestrogen receptor |
PR | Progesterone receptor |
TNBC | Triple-negative breast cancer |
DFS | Disease-free survival |
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Variables | Groups | |||||||
---|---|---|---|---|---|---|---|---|
Age (years) | mean: 59.1; | <50: 33 (22.6%); | ≥50: 113 (77.4%) | |||||
T category | pT1mic: 10 (6.8%) | pT1a: 10 (6.8%) | pT1b: 38 (26%) | pT1c: 82 (56.2%) | pT2: 6 (4.1%) | |||
N category | N0: 143 (97.9%) | N1: 3 (2.1%) | ||||||
Stage | UICC I: 134 (91.8%) | UICC II: 12 (8.2%) | ||||||
Tumour size (mm) | <10: 40 (27.4%); | 10–20: 96 (65.8%); | >20: 10 (6.8%) | |||||
Histological grading | G1: 38 (26%) | G2: 101 (69.2%) | G3: 4 (2.7%) | n.a. 3 (2.1%) | ||||
Histological typing | lobular: 23 (15.8%) | no special type: 100 (68.5%) | other: 23 (15.8%) | |||||
Ki67 | <20: 110 (75.3%) | ≥20: 32 (21.9%) | n.a. 4 (2.7%) | |||||
Oestrogen receptor status | positive: 141 (96.6%) | negative: 1 (0.7%) | n.a. 4 (2.7%) | |||||
Progesterone receptor status | positive: 132 (90.4%) | negative: 11 (7.5%) | n.a. 3 (2.1%) | |||||
Her2 status | positive: 8 (5.5%) | negative: 133 (91.1%) | n.a. 5 (3.4%) | |||||
Molecular subtype | Luminal A: 97 (66.4%) | Luminal B: 44 (30.1%) | n.a. 5 (3.4%) | |||||
Hormone therapy | Yes: 131 (89.7%) | No: 15 (10.3%) | ||||||
Chemotherapy | Yes: 10 (6.8%) | No: 136 (93.2%) |
CD20+ TIIC Densities Normal Tissue | CD20+ TIIC Densities | |||||
---|---|---|---|---|---|---|
Proximity | Distant | Central Tumour | Invasive Front | |||
Correlation coefficient | CD4+ TIIC densities normal tissue (prox) | 0.139 | 0.080 | CD4+ TIIC densities central tumour | 0.521 | 0.193 |
p | 0.192 | 0.459 | <0.001 | 0.038 | ||
n | 90 | 89 | 122 | 116 | ||
Correlation coefficient | CD4+ TIIC densities normal tissue (dist) | 0.126 | 0.081 | CD4+ TIIC densities invasive front | 0.179 | 0.397 |
p | 0.248 | 0.373 | 0.049 | <0.001 | ||
n | 86 | 123 | 121 | 128 |
Stromal (n = 134) | Intraepithelial (n = 111) | ||||||
---|---|---|---|---|---|---|---|
N (total) | CD45RO+ Tiics Low | CD45RO+ TIICs High | p | CD45RO+ TIICs Low | CD45RO+ TIICs High | p | |
Age (years) | 0.02 | 0.21 | |||||
<50 | 33 | 1 (4%) | 26 (24%) | 16 (18%) | 6 (30%) | ||
≥50 | 113 | 25 (96%) | 82 (76%) | 75 (82%) | 14 (70%) | ||
Tumour size (mm) | 0.43 | 0.49 | |||||
<20 | 136 | 25 (96%) | 99 (92%) | 82 (90%) | 19 (95%) | ||
≥20 | 10 | 1 (4%) | 9 (8%) | 9 (10%) | 1 (5%) | ||
Histological grading | 0.57 | 0.49 | |||||
G1 | 38 | 6 (23%) | 30 (29%) | 24 (27%) | 7 (35%) | ||
G2 + G3 | 105 | 20 (77%) | 75 (71%) | 64 (73%) | 13 (65%) | ||
n.a. | 3 | ||||||
Histological typing | 0.94 | 0.01 | |||||
nonlobular | 123 | 22 (85%) | 92 (85%) | 83 (91%) | 14 (70%) | ||
lobular | 23 | 4 (15%) | 16 (15%) | 8 (9%) | 6 (30%) | ||
Ki67 | 0.38 | 0.43 | |||||
<20 | 110 | 18 (72%) | 84 (80%) | 67 (77%) | 17 (85%) | ||
≥20 | 32 | 7 (28%) | 21 (20%) | 20 (23%) | 3 (15%) | ||
n.a. | 4 | ||||||
ER status | 0.62 | 0.63 | |||||
neg | 1 | 0 (0%) | 1 (1%) | 1 (1%) | 0 (0%) | ||
pos | 141 | 25 (100%) | 104 (99%) | 86 (99%) | 20 (100%) | ||
n.a. | 4 | ||||||
PR status | 0.13 | 0.47 | |||||
neg | 11 | 4 (16%) | 7 (7%) | 9 (10%) | 1 (5%) | ||
pos | 132 | 21 (84%) | 99 (93%) | 79 (90%) | 19 (95%) | ||
n.a. | 3 | ||||||
Her2 status | 0.67 | 0.94 | |||||
neg | 133 | 23 (92%) | 99 (94%) | 83 (95%) | 19 (95%) | ||
pos | 8 | 2 (8%) | 6 (6%) | 4 (5%) | 1 (5%) | ||
n.a. | 5 | ||||||
Subtype | 0.12 | 0.23 | |||||
Luminal A | 97 | 14 (56%) | 75 (72%) | 57 (66%) | 16 (80%) | ||
Luminal B | 44 | 11 (44%) | 29 (28%) | 29 (34%) | 4 (20%) | ||
n.a. | 5 |
Breast Cancer | Univariate Analysis | Multivariate Analysis | ||||
---|---|---|---|---|---|---|
Variable | Hazard Ratio | 95% C.I. | p | Hazard Ratio | 95% C.I. | p |
Age (years) (<50 (n = 28) vs ≥50 (n = 118)) | 1.009 | 0.339–3.002 | 0.988 | --- | --- | --- |
Stage (UICC I (n = 134) vs UICC II (n = 12 )) | 1.934 | 0.569–6.576 | 0.291 | --- | --- | --- |
Tumour size (mm) (<20 (n = 136) vs ≥20 (n = 10)) | 1.379 | 0.321–5.927 | 0.666 | --- | --- | --- |
Histological grading (G1 (n = 38) vs G2-3 (n = 105)) | 3.344 | 0.779–14.365 | 0.105 | 2.216 | 0.257–19.103 | 0.469 |
Histological typing (nonlobular (n = 123) vs lobular (n = 23)) | 0.722 | 0.211–2.471 | 0.603 | --- | --- | --- |
DCIS (no (n = 76) vs yes (n = 57)) | 0.798 | 0.312–2.04 | 0.637 | --- | --- | --- |
Ki67 (<20 (n = 110) vs ≥20 (n = 32)) | 2.563 | 1.077–6.098 | 0.033 | 5.973 | 1.677–21.278 | 0.006 |
Her2 status (negative (n = 133) vs positive (n = 8)) | 0.890 | 0.119–6.66 | 0.910 | --- | --- | --- |
Luminal (A (n = 97) vs B (n = 44)) | 2.182 | 0.925–5.147 | 0.075 | 0.273 | 0.024–3.137 | 0.298 |
Hormone therapy (no (n = 15) vs yes (n = 131)) | 1.003 | 0.234–4.309 | 0.996 | --- | --- | --- |
Chemotherapy (no (n = 136) vs yes (n = 10 )) | 2.280 | 0.67–7.763 | 0.187 | --- | --- | --- |
Stromal CD4+ TIICs (low (n = 59) vs high (n = 75)) | 2.712 | 0.899–8.185 | 0.077 | 1.250 | 0.154–10.156 | 0.834 |
Intraepithelial CD4+ TIICs (low (n = 86) vs high (n = 25)) | 5.467 | 1.963–15.226 | 0.001 | 2.869 | 0.929–8.857 | 0.067 |
Stromal CD45RO+ TIICs (low (n = 26) vs high (n = 108)) | 0.243 | 0.098–0.599 | 0.002 | 0.104 | 0.027–0.398 | 0.001 |
Intraepithelial CD45RO+ TIICs (low (n = 91) vs high (n = 20)) | 0.854 | 0.191–3.816 | 0.836 | --- | --- | --- |
Stromal CD1a+ TIICs (low (n = 106) vs high (n = 22)) | 0.545 | 0.124–2.398 | 0.422 | --- | --- | --- |
Intraepithelial CD1a+ TIICs (low (n = 58) vs high (n = 47)) | 0.688 | 0.241 - 1.968 | 0.486 | --- | --- | --- |
Stromal CD20+ TIICs (low (n = 76) vs high (n = 52)) | 2.535 | 0.935–6.872 | 0.067 | 11.601 | 2.485–54.152 | 0.002 |
Intraepithelial CD20+ TIICs (low (n = 74) vs high (n = 31)) | 2.132 | 0.771–5.891 | 0.144 | 0.619 | 0.129–2.969 | 0.549 |
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Schnellhardt, S.; Erber, R.; Büttner-Herold, M.; Rosahl, M.-C.; Ott, O.J.; Strnad, V.; Beckmann, M.W.; King, L.; Hartmann, A.; Fietkau, R.; et al. Tumour-Infiltrating Inflammatory Cells in Early Breast Cancer: An Underrated Prognostic and Predictive Factor? Int. J. Mol. Sci. 2020, 21, 8238. https://doi.org/10.3390/ijms21218238
Schnellhardt S, Erber R, Büttner-Herold M, Rosahl M-C, Ott OJ, Strnad V, Beckmann MW, King L, Hartmann A, Fietkau R, et al. Tumour-Infiltrating Inflammatory Cells in Early Breast Cancer: An Underrated Prognostic and Predictive Factor? International Journal of Molecular Sciences. 2020; 21(21):8238. https://doi.org/10.3390/ijms21218238
Chicago/Turabian StyleSchnellhardt, Sören, Ramona Erber, Maike Büttner-Herold, Marie-Charlotte Rosahl, Oliver J. Ott, Vratislav Strnad, Matthias W. Beckmann, Lillian King, Arndt Hartmann, Rainer Fietkau, and et al. 2020. "Tumour-Infiltrating Inflammatory Cells in Early Breast Cancer: An Underrated Prognostic and Predictive Factor?" International Journal of Molecular Sciences 21, no. 21: 8238. https://doi.org/10.3390/ijms21218238