Background
Methods
Patients and study design
Characteristics | Total (n = 187) | MACC1 tumor center N (%); (n = 187) | P-value | |
---|---|---|---|---|
Low (Score 0) | High (Score 1–3) | |||
N = 78 (41.7%) | N = 109 (58.3%) | |||
Age (yrs.)
| ||||
Mean (min, max) | 68.6 (35–93) | 69.2 (36–93) | 68.1 (35–91) | 0.1732 |
Tumor size (cm)
| ||||
Mean (min, max) | 4.5 (1.2–12) | 4.8 (2–12) | 4.3 (1.2–8) | 0.5723 |
Gender
| ||||
Male | 88 (47.3) | 35 (44.9) | 53 (49.1) | 0.5711 |
Female | 98 (52.7) | 43 (55.1) | 55 (50.9) | |
Histological subtype
| ||||
Non-mucinous | 167 (89.3) | 70 (89.7) | 97 (89.0) | 0.8695 |
Mucinous | 20 (10.7) | 8 (10.3) | 12 (11.0) | |
Tumor grade
| ||||
G1-2 | 120 (64.2) | 55 (70.5) | 65 (59.6) | 0.126 |
G3 | 67 (35.8) | 23 (29.5) | 44 (40.4) | |
Tumor location
| ||||
Left | 113 (60.7) | 42 (53.9) | 71 (65.7) | 0.2027 |
Rectum | 21 (11.3) | 9 (11.5) | 12 (11.1) | |
Right | 52 (28.0) | 27 (34.6) | 25 (23.2) | |
pT
| ||||
pT1 + pT2 | 47 (25.1) | 26 (33.3) | 21 (19.3) | 0.0288 |
pT3 + pT4 | 140 (74.9) | 52 (66.7) | 88 (80.7) | |
pN
| ||||
pN0 | 97 (51.9) | 51 (65.4) | 46 (42.2) | 0.0018 |
pN1-2 | 90 (48.1) | 27 (34.6) | 63 (57.8) | |
pM
| ||||
pM0 | 167 (89.8) | 73 (93.6) | 94 (87.0) | 0.1454 |
pM1 | 19 (10.2) | 5 (6.4) | 14 (13.0) | |
TNM stage
| ||||
Stage I | 40 (21.5) | 26 (33.3) | 14 (13.0) | 0.0023 |
Stage II | 53 (28.5) | 24 (30.8) | 29 (26.9) | |
Stage III | 74 (39.8) | 23 (29.5) | 51 (47.2) | |
Stage IV | 19 (10.2) | 5 (6.4) | 14 (13.0) | |
Tumor budding
| ||||
Low-grade | 101 (54.0) | 54 (69.2) | 47 (43.1) | 0.0004 |
High-grade | 86 (46.0) | 24 (30.8) | 62 (56.9) | |
Venous invasion
| ||||
Present | 32 (17.1) | 8 (10.3) | 24 (22.0) | 0.0352 |
Absent | 155 (82.9) | 70 (89.7) | 85 (78.0) | |
Lymphatic invasion
| ||||
Present | 74 (39.6) | 24 (30.8) | 50 (45.9) | 0.0373 |
Absent | 113 (60.4) | 54 (69.2) | 59 (54.1) | |
Therapy
| ||||
Untreated | 66 (35.3) | 39 (50.0) | 27 (24.8) | 0.0004 |
Treated | 121 (64.7) | 39 (50.0) | 82 (75.2) | |
MMR status
| ||||
Proficient | 170 (91.4) | 71 (91.0) | 99 (91.7) | 0.8777 |
Deficient | 16 (8.6) | 7 (9.0) | 9 (8.3) | |
KRAS status
| ||||
Wild-type | 124 (67.0) | 54 (70.1) | 70 (64.8) | 0.4484 |
Mutation | 61 (33.0) | 23 (29.9) | 38 (35.2) | |
BRAF status
| ||||
Wild-type | 165 (91.2) | 69 (92.0) | 96 (90.6) | 0.7378 |
Mutation | 16 (8.8) | 6 (8.0) | 10 (9.4) | |
CIMP status
| ||||
Negative/Low | 90 (87.4) | 40 (90.9) | 50 (84.8) | 0.3887 |
High | 13 (12.6) | 4 (9.1) | 9 (15.3) | |
Survival rate
| ||||
Median | 60 (50-ne) | Not reached | 58 (43-ne) | 0.2585 |
Ethics committee approval
Tissue sections and MACC1 immunohistochemistry
Evaluation of MACC1
KRAS, BRAF and MMR status
Statistical analysis
Results
Geographic analysis of MACC1 expression
MACC1 expression in the tumor center
MACC1 expression at the invasive front
Characteristics | MACC1 tumor front N (%); (n = 187) | P-value | MACC1 tumor buds N (%); (n = 187) | P-value | ||
---|---|---|---|---|---|---|
Low (Score 0) | High (Score 1–3) | Low (<median) | High (>median) | |||
Age (yrs.)
| ||||||
Mean (min, max) | 69.9 (38–88) | 68.1 (35–93) | 0.1141 | 70.1 (36–89) | 67.6 (41–91) | 0.0408 |
Tumor size (cm)
| ||||||
Mean (min, max) | 5.0 (2–12) | 4.4 (1.2–8.0) | 0.4457 | 4.6 (2–12) | 4.5 (1.2–8) | 0.7134 |
Gender
| ||||||
Male | 18 (35.3) | 70 (51.9) | 0.0436 | 23 (46.0) | 32 (45.1) | 0.9195 |
Female | 33 (64.7) | 65 (48.2) | 27 (54.0) | 39 (54.9) | ||
Histological subtype
| ||||||
Non-mucinous | 46 (90.2) | 121 (89.0) | 0.8092 | 45 (90.0) | 61 (85.9) | 0.502 |
Mucinous | 5 (9.8) | 15 (11.0) | 5 (10.0) | 10 (14.1) | ||
Tumor grade
| ||||||
G1-2 | 36 (70.6) | 84 (61.8) | 0.2624 | 30 (60.0) | 35 (49.3) | 0.2449 |
G3 | 15 (29.4) | 52 (38.2) | 20 (40.0) | 36 (50.7) | ||
Tumor location
| ||||||
Left | 27 (52.9) | 86 (63.7) | 0.3547 | 30 (60.0) | 43 (61.4) | 0.7867 |
Rectum | 6 (11.8) | 15 (11.1) | 7 (14.0) | 7 (10.0) | ||
Right | 18 (35.3) | 34 (25.2) | 13 (26.0) | 20 (28.6) | ||
pT
| ||||||
pT1 + pT2 | 22 (43.1) | 25 (18.4) | 0.0005 | 15 (30.0) | 3 (4.2) | <0.0001 |
pT3 + pT4 | 29 (56.9) | 111 (81.6) | 35 (70.0) | 68 (95.8) | ||
pN
| ||||||
pN0 | 38 (74.5) | 59 (43.4) | 0.0001 | 26 (52.0) | 24 (33.8) | 0.0453 |
pN1-2 | 13 (25.5) | 77 (56.6) | 24 (48.0) | 47 (66.2) | ||
pM
| ||||||
pM0 | 50 (98.0) | 117 (86.7) | 0.0223 | 47 (94.0) | 60 (85.7) | 0.1499 |
pM1 | 1 (2.0) | 18 (13.3) | 3 (6.0) | 10 (14.3) | ||
TNM stage
| ||||||
Stage I | 22 (43.1) | 18 (13.3) | <0.0001 | 13 (26.0) | 1 (1.4) | 0.0004 |
Stage II | 15 (29.4) | 38 (282.) | 12 (24.0) | 20 (28.6) | ||
Stage III | 13 (25.5) | 61 (45.2) | 22 (44.0) | 39 (55.7) | ||
Stage IV | 1 (2.0) | 18 (13.3) | 3 (6.0) | 10 (14.3) | ||
Tumor budding
| ||||||
Low-grade | 38 (74.5) | 63 (46.3) | 0.0006 | 28 (56.0) | 20 (28.2) | 0.0021 |
High-grade | 13 (25.5) | 73 (53.7) | 22 (44.0) | 51 (71.8) | ||
Venous invasion
| ||||||
Present | 3 (5.9) | 29 (21.3) | 0.0125 | 7 (14.0) | 19 (26.8) | 0.0924 |
Absent | 48 (94.1) | 107 (78.7) | 43 (86.0) | 52 (73.2) | ||
Lymphatic invasion
| ||||||
Present | 11 (21.6) | 63 (46.3) | 0.002 | 24 (48.0) | 38 (53.5) | 0.5496 |
Absent | 40 (78.4) | 73 (53.7) | 26 (52.0) | 33 (46.5) | ||
Therapy
| ||||||
Untreated | 29 (56.9) | 37 (27.2) | 0.0002 | 24 (48.0) | 9 (12.7) | <0.0001 |
Treated | 22 (43.1) | 99 (72.8) | 26 (52.0) | 62 (87.3) | ||
MMR status
| ||||||
Proficient | 44 (86.3) | 126 (93.3) | 0.1256 | 46 (92.0) | 63 (90.0) | 0.7607 |
Deficient | 7 (13.7) | 9 (6.7) | 4 (8.0) | 7 (10.0) | ||
KRAS status
| ||||||
Wild-type | 32 (64.0) | 92 (68.2) | 0.594 | 33 (66.0) | 46 (65.7) | 0.974 |
Mutation | 18 (36.0) | 43 (31.9) | 17 (34.0) | 24 (34.3) | ||
BRAF status
| ||||||
Wild-type | 45 (90.0) | 120 (91.6) | 0.772 | 44 (89.8) | 60 (89.6) | 0.966 |
Mutation | 5 (10.0) | 11 (8.4) | 5 (10.2) | 7 (10.5) | ||
CIMP status
| ||||||
Negative/Low | 27 (90.0) | 63 (86.3) | 0.7514 | 21 (84.0) | 36 (83.7) | 1.0 |
High | 3 (10.0) | 10 (13.7) | 4 (16.0) | 7 (16.3) | ||
Survival rate
| ||||||
Median | Not reached | 58 (43-ne) | 0.0217 | 53.0 (43–61) | 55.0 (36-ne) | 0.839 |
Parameter | HR (95%CI) | P-value | |
---|---|---|---|
MACC1
| |||
Low (Score 0) | 1.0 | 0.7827 | |
High (Score 1–3) | 1.1 (0.56-2.16) | ||
pT
| |||
pT1-2 | 1.0 | 0.3425 | |
pT3-4 | 1.52 (0.64-3.57) | ||
pN
| |||
pN0 | 1.0 | 0.0003 | |
pN1-2 | 3.48 (1.77-6.85) | ||
pM
| |||
pM0 | 1.0 | <0.0001 | |
pM1 | 4.12 (2.2-7.68) | ||
Adjuvant therapy
| |||
None | 1.0 | 0.3284 | |
Treated | 0.74 (0.4-1.36) |