Introduction
Methods
Clinical samples and histology analysis
Immune infiltrate scores
Other statistical methods
Results
Immune-cancer cell colocalization was independent of known parameters of breast cancer
Characteristics | All subtypes (discovery) | All subtypes (validation) | Her2+ (discovery) | HER2+ (validation) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Morisita high | Morisita low |
P
| Morisita high | Morisita low |
P
| Morisita high | Morisita low |
P
| Morisita high | Morisita low |
P
| ||
Number | 316 | 170 | 377 | 139 | 42 | 34 | 37 | 20 | |||||
Follow up (months) | 117.7 (4.9–120) | 110.3 (4.2–120) | 64.8 (0.3–120) | 50.5 (1.9–120) | 108.1 (21.2–120) | 61.5 (6.8–120) | 62.3 (1.8–120) | 36.3 (10–88.4) | |||||
Age, years | 59.8 (27.6–86.1) | 59.3 (21.9–83.4) | 0.38 | 60.8 (30–92.1) | 60.9 (26.4–96.3) | 0.81 | 57 (28.4–80.6) | 54.2 (21.9–71) | 0.23 | 57.4 (33.6–87) | 55.9 (35.9–87.2) | 0.65 | |
Death | No | 246 (77.8 %) | 113 (66.5 %) | 0.0074* | 334 (88.6 %) | 115 (82.7 %) | 0.1 | 25 (59.5 %) | 14 (41.2 %) | 0.097 | 35 (94.6 %) | 13 (65 %) | 0.0063* |
Yes | 64 (20.3 %) | 53 (31.2 %) | 43 (11.4 %) | 24 (17.3 %) | 14 (33.3 %) | 19 (55.9 %) | 2 (5.4 %) | 7 (35 %) | |||||
Size | <2 cm | 122 (38.6 %) | 66 (38.8 %) | 0.88 | 120 (31.8 %) | 41 (29.5 %) | 0.27 | 9 (21.4 %) | 13 (38.2 %) | 0.15 | 9 (24.3 %) | 9 (45 %) | 0.056 |
>2 cm, <5 cm | 177 (56 %) | 97 (57.1 %) | 226 (59.9 %) | 80 (57.6 %) | 30 (71.4 %) | 17 (50 %) | 24 (64.9 %) | 7 (35 %) | |||||
>5 cm | 17 (5.4 %) | 7 (4.1 %) | 29 (7.7 %) | 17 (12.2 %) | 3 (7.1 %) | 4 (11.8 %) | 3 (8.1 %) | 4 (20 %) | |||||
Node | Neg (pN0) | 153 (48.4 %) | 84 (49.4 %) | 0.85 | 180 (47.7 %) | 57 (41 %) | 0.19 | 19 (45.2 %) | 10 (29.4 %) | 0.23 | 15 (40.5 %) | 9 (45 %) | 0.78 |
Pos (pN1-pN3) | 163 (51.6 %) | 86 (50.6 %) | 193 (51.2 %) | 80 (57.6 %) | 23 (54.8 %) | 24 (70.6 %) | 22 (59.5 %) | 11 (55 %) | |||||
Grade | 1 | 37 (11.7 %) | 18 (10.6 %) | 0.39 | 42 (11.1 %) | 9 (6.5 %) | 0.069 | 1 (2.4 %) | 0 (0 %) | 1 | 2 (5.4 %) | 0 (0 %) | 0.86 |
2 | 120 (38 %) | 56 (32.9 %) | 123 (32.6 %) | 59 (42.4 %) | 8 (19 %) | 7 (20.6 %) | 6 (16.2 %) | 3 (15 %) | |||||
3 | 149 (47.2 %) | 92 (54.1 %) | 192 (50.9 %) | 64 (46 %) | 32 (76.2 %) | 27 (79.4 %) | 26 (70.3 %) | 15 (75 %) | |||||
ER | Neg | 76 (24.1 %) | 54 (31.8 %) | 0.069 | 82 (21.8 %) | 39 (28.1 %) | 0.16 | 22 (52.4 %) | 19 (55.9 %) | 0.82 | 14 (37.8 %) | 14 (70 %) | 0.028* |
Pos | 240 (75.9 %) | 116 (68.2 %) | 295 (78.2 %) | 100 (71.9 %) | 20 (47.6 %) | 15 (44.1 %) | 23 (62.2 %) | 6 (30 %) | |||||
Her2 | Not amplified | 271 (85.8 %) | 139 (81.8 %) | 0.29 | 335 (88.9 %) | 123 (88.5 %) | 0.87 | 42 (100 %) | 34 (100 %) | NA | 37 (100 %) | 20 (100 %) | NA |
Amplified | 45 (14.2 %) | 31 (18.2 %) | 41 (10.9 %) | 16 (11.5 %) | 20 (47.6 %) | 14 (41.2 %) | 24 (64.9 %) | 6 (30 %) | |||||
TP53
| WT | 224 (70.9 %) | 110 (64.7 %) | 0.076 | 252 (66.8 %) | 94 (67.6 %) | 1 | 20 (47.6 %) | 20 (58.8 %) | 0.49 | 7 (18.9 %) | 10 (50 %) | 0.011* |
Mutated | 83 (26.3 %) | 59 (34.7 %) | 94 (24.9 %) | 35 (25.2 %) | 9 (21.4 %) | 28 (82.4 %) | 7 (18.9 %) | 14 (70 %) | |||||
IA | Low | 89 (28.2 %) | 148 (87.1 %) | 1.1×10−37* | 71 (18.8 %) | 111 (79.9 %) | 1.5×10−37* | 33 (78.6 %) | 6 (17.6 %) | 1.6×10−7* | 30 (81.1 %) | 6 (30 %) | 0.00036* |
High | 227 (71.8 %) | 22 (12.9 %) | 306 (81.2 %) | 28 (20.1 %) | 4 (9.5 %) | 4 (11.8 %) | 5 (13.5 %) | 2 (10 %) | |||||
Pam50 | Basal | 54 (17.1 %) | 43 (25.3 %) | 0.15 | 57 (15.1 %) | 21 (15.1 %) | 0.45 | 25 (59.5 %) | 16 (47.1 %) | 0.83 | 13 (35.1 %) | 9 (45 %) | 0.46 |
HER2 | 50 (15.8 %) | 18 (10.6 %) | 30 (8 %) | 12 (8.6 %) | 5 (11.9 %) | 4 (11.8 %) | 7 (18.9 %) | 1 (5 %) | |||||
LumA | 106 (33.5 %) | 49 (28.8 %) | 129 (34.2 %) | 50 (36 %) | 6 (14.3 %) | 7 (20.6 %) | 9 (24.3 %) | 4 (20 %) | |||||
LumB | 86 (27.2 %) | 48 (28.2 %) | 103 (27.3 %) | 28 (20.1 %) | 2 (4.8 %) | 3 (8.8 %) | 3 (8.1 %) | 4 (20 %) | |||||
Normal | 19 (6 %) | 11 (6.5 %) | 58 (15.4 %) | 28 (20.1 %) | 42 | 34 | 37 | 20 |
Immune-cancer cell colocalization measured by the Morisita-Horn ecological index is associated with good prognosis in unselected breast cancer
Immune-cancer cell colocalization is associated with a good prognosis in Her2+ and luminal A tumors
Hazard ratio (95 % CI) |
P value | Conc | Hazard ratio (95 % CI) |
P value | Conc | ||
---|---|---|---|---|---|---|---|
All breast cancers | Discovery cohort (475 samples) | Validation cohort (514 samples) | |||||
Morisita | 0.6 (0.42–0.86) |
0.0052
| 0.56 | 0.41 (0.25–0.7) |
0.00067
| 0.75 | |
Lymphnode | 2.36 (1.62–3.46) | 9.4×10−6
| 0.607 | 3.55 (1.92–6.56) | 5.4×10−5
| 0.73 | |
Size | 2.26 (1.63–3.13) | 8.9×10−7
| 0.612 | 2.42 (1.57–3.73) | 6.5×10−5
| 0.74 | |
Grade | 2.18 (1.59–3.01) | 1.8×10−6
| 0.627 | 2.76 (1.66–4.59) | 9.6×10−5
| 0.619 | |
Morisita | 0.59 (0.41–0.85) |
0.005
| 0.699 | 0.4 (0.24–0.69) |
0.00085
| 0.9 | |
Lymphnode | 1.78 (1.19–2.65) | 0.0046 | 2.2 (1.16–4.17) | 0.015 | |||
Size | 1.89 (1.34–2.68) | 0.00033 | 1.88 (1.17–3.03) | 0.0096 | |||
Grade | 1.82 (1.31–2.53) | 0.00035 | 2.58 (1.53–4.34) | 0.00038 | |||
Luminal A | Discovery cohort (150 samples) | Validation cohort (178 samples) | |||||
Morisita | 0.13 (0.04–0.45) |
0.00014
| 0.715 | 0.29 (0.07–1.14) | 0.059 | 0.618 | |
Lymphnode | 1.43 (0.46–4.42) | 0.54 | 0.552 | 1.93 (0.5–7.47) | 0.33 | 0.576 | |
Size | 4.38 (1.46–13.14) | 0.0067 | 0.692 | 2.13 (0.69–6.62) | 0.19 | 0.58 | |
Grade | 1.84 (0.83–4.1) | 0.13 | 0.619 | 2.47 (0.9–6.79) | 0.071 | 0.62 | |
Morisita | 0.15 (0.04–0.53) |
0.003
| 0.839 | 0.33 (0.08–1.31) | 0.11 | 0.733 | |
Lymphnode | 1.01 (0.3–3.41) | 0.98 | 1.18 (0.29–4.8) | 0.81 | |||
Size | 4.17 (0.99–17.56) | 0.052 | 2.09 (0.54–8.14) | 0.29 | |||
Grade | 1.44 (0.61–3.42) | 0.41 | 2.47 (0.86–7.13) | 0.095 | |||
Her2 by PAM50 | Discovery cohort (65 samples) | Validation cohort (42 samples) | |||||
Morisita | 0.29 (0.15–0.57) |
0.00017
| 0.65 | 0.12 (0.02–0.61) |
0.0022
| 0.808 | |
Lymphnode | 3.59 (1.55–8.3) | 0.0015 | 0.64 | NA | 0.0098 | 0.666 | |
Size | 1.74 (0.97–3.12) | 0.064 | 0.577 | 4.83 (1.48–15.78) | 0.0051 | 0.689 | |
Grade | 1.68 (0.78–3.62) | 0.18 | 0.574 | 0.29 (0.07–1.23) | 0.075 | 0.529 | |
Morisita | 0.38 (0.17–0.84) |
0.016
| 0.734 | 0.1 (0.01–0.66) |
0.017
| 0.896 | |
Lymphnode | 2.2 (0.87–5.57) | 0.095 | NA | 1 | |||
Size | 1.47 (0.83–2.61) | 0.18 | 0.78 (0.16–3.83) | 0.76 | |||
Grade | 1.8 (0.81–4.02) | 0.15 | 0.37 (0.08–1.74) | 0.21 | |||
Her2+ by SNP6 | Discovery cohort (72 samples) | Validation cohort (56 samples) | |||||
Morisita | 0.49 (0.25–0.98) |
0.039
| 0.597 | 0.05 (0.01–0.4) |
9.3×10
−5
| 0.808 | |
Lymphnode | 3.31 (1.5–7.31) | 0.0017 | 0.637 | 7.31 (0.89–59.98) | 0.031 | 0.666 | |
Size | 1.49 (0.82–2.73) | 0.19 | 0.557 | 3.52 (1–12.36) | 0.05 | 0.689 | |
Grade | 1.56 (0.68–3.59) | 0.29 | 0.551 | 1.41 (0.36–5.58) | 0.62 | 0.529 | |
Morisita | 0.44 (0.21–0.91) |
0.027
| 0.722 | 0.03 (0–0.3) |
0.0031
| 0.896 | |
Lymphnode | 3.68 (1.49–9.09) | 0.0048 | 2.65 (0.28–24.99) | 0.39 | |||
Size | 2.01 (1–4.04) | 0.049 | 3.42 (1.1–10.64) | 0.034 | |||
Grade | 1.46 (0.57–3.75) | 0.43 | 1.86 (0.33–10.42) | 0.48 |