Table 1 Clinical, pathological and molecular characteristics of colorectal cancer cases according to the intratumoural periglandular reaction to colorectal cancer and tumour-infiltrating lymphocytes.
Intratumoural periglandular reaction | Tumour-infiltrating lymphocytes | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
Characteristica | No. of cases (N = 1462) | Negative/low (N = 193) | Intermediate (N = 1085) | High (N = 184) | P-valueb | No. of cases (N = 1461) | Negative/low (N = 1095) | Intermediate (N = 219) | High (N = 147) | P-valueb |
Sex | 0.51 | 0.0039 | ||||||||
Female (NHS) | 820 (56%) | 114 (59%) | 599 (55%) | 107 (58%) | 821 (56%) | 588 (54%) | 139 (63%) | 94 (64%) | ||
Male (HPFS) | 642 (44%) | 79 (41%) | 486 (45%) | 77 (42%) | 640 (44%) | 507 (46%) | 80 (37%) | 53 (36%) | ||
Mean age ± SD (years) | 69.0 ± 9.0 | 70.3 ± 9.2 | 68.4 ± 9.0 | 71.1 ± 8.1 | <0.0001 | 69.0 ± 9.0 | 68.5 ± 9.0 | 70.5 ± 8.8 | 70.3 ± 8.4 | 0.0017 |
Year of diagnosis | <0.0001 | 0.0076 | ||||||||
1995 or before | 520 (36%) | 32 (17%) | 445 (41%) | 43 (23%) | 520 (36%) | 411 (38%) | 60 (27%) | 49 (33%) | ||
1996–2000 | 440 (30%) | 44 (23%) | 337 (31%) | 59 (32%) | 439 (30%) | 324 (30%) | 63 (29%) | 52 (35%) | ||
2001–2008 | 502 (34%) | 117 (61%) | 303 (28%) | 82 (45%) | 502 (34%) | 360 (33%) | 96 (44%) | 46 (31%) | ||
Family history of colorectal cancer in first-degree relative(s) | 0.44 | 0.26 | ||||||||
Absent | 1174 (81%) | 160 (83%) | 871 (81%) | 143 (78%) | 1172 (80%) | 889 (81%) | 169 (78%) | 114 (78%) | ||
Present | 283 (19%) | 33 (17%) | 209 (19%) | 41 (22%) | 284 (20%) | 202 (19%) | 49 (22%) | 33 (22%) | ||
Tumour location | <0.0001 | <0.0001 | ||||||||
Caecum | 256 (18%) | 21 (11%) | 197 (18%) | 38 (21%) | 256 (18%) | 171 (16%) | 51 (23%) | 34 (23%) | ||
Ascending to transverse colon | 447 (31%) | 67 (35%) | 298 (28%) | 82 (45%) | 446 (31%) | 280 (26%) | 85 (39%) | 81 (55%) | ||
Descending to sigmoid colon | 439 (30%) | 62 (32%) | 333 (31%) | 44 (24%) | 440 (30%) | 366 (34%) | 48 (22%) | 26 (18%) | ||
Rectum | 314 (22%) | 41 (21%) | 253 (23%) | 20 (11%) | 313 (22%) | 273 (25%) | 34 (16%) | 6 (4.1%) | ||
AJCC disease stage | <0.0001 | <0.0001 | ||||||||
I | 343 (26%) | 29 (17%) | 258 (26%) | 56 (33%) | 343 (26%) | 248 (25%) | 58 (29%) | 37 (26%) | ||
II | 427 (32%) | 46 (26%) | 310 (32%) | 71 (42%) | 427 (32%) | 289 (29%) | 65 (33%) | 73 (52%) | ||
III | 371 (28%) | 53 (30%) | 282 (29%) | 36 (21%) | 370 (28%) | 290 (29%) | 56 (28%) | 24 (17%) | ||
IV | 184 (14%) | 46 (26%) | 131 (13%) | 7 (4.1%) | 185 (14%) | 158 (16%) | 21 (11%) | 6 (4.3%) | ||
Tumour differentiation | <0.0001 | <0.0001 | ||||||||
Well to moderate | 1,299 (90%) | 173 (90%) | 992 (92%) | 134 (73%) | 1,298 (90%) | 1,017 (94%) | 183 (84%) | 98 (67%) | ||
Poor | 151 (10%) | 19 (9.9%) | 82 (7.6%) | 50 (27%) | 151 (10%) | 66 (6.1%) | 36 (16%) | 49 (33%) | ||
MSI status | <0.0001 | <0.0001 | ||||||||
Non-MSI-high | 881 (83%) | 137 (92%) | 669 (87%) | 75 (54%) | 881 (83%) | 729 (93%) | 111 (66%) | 41 (38%) | ||
MSI-high | 176 (17%) | 12 (8.1%) | 100 (13%) | 64 (46%) | 176 (17%) | 52 (6.7%) | 58 (34%) | 66 (62%) | ||
CIMP status | <0.0001 | <0.0001 | ||||||||
Low/negative | 832 (82%) | 129 (89%) | 635 (86%) | 68 (53%) | 832 (82%) | 695 (92%) | 96 (62%) | 41 (41%) | ||
High | 183 (18%) | 16 (11%) | 106 (14%) | 61 (47%) | 183 (18%) | 63 (8.3%) | 60 (38%) | 60 (59%) | ||
Mean LINE-1 methylation level ± SD (%) | 63.2 ± 9.9 | 63.9 ± 10.2 | 62.6 ± 9.7 | 66.4 ± 10.6 | <0.0001 | 63.2 ± 9.9 | 62.5 ± 9.8 | 64.8 ± 9.4 | 65.7 ± 10.8 | 0.0001 |
KRAS mutation | 0.12 | 0.028 | ||||||||
Wild type | 586 (58%) | 72 (52%) | 435 (58%) | 79 (65%) | 586 (58%) | 421 (56%) | 94 (61%) | 71 (69%) | ||
Mutant | 423 (42%) | 66 (48%) | 314 (42%) | 43 (35%) | 423 (42%) | 332 (44%) | 59 (39%) | 32 (31%) | ||
BRAF mutation | <0.0001 | <0.0001 | ||||||||
Wild type | 893 (84%) | 128 (86%) | 672 (87%) | 93 (68%) | 893 (84%) | 709 (90%) | 122 (73%) | 62 (58%) | ||
Mutant | 167 (16%) | 20 (14%) | 103 (13%) | 44 (32%) | 167 (16%) | 77 (9.8%) | 45 (27%) | 45 (42%) | ||
PIK3CA mutation | 0.38 | 0.82 | ||||||||
Wild type | 829 (84%) | 118 (82%) | 609 (85%) | 102 (80%) | 829 (84%) | 614 (83%) | 133 (85%) | 82 (85%) | ||
Mutant | 161 (16%) | 26 (18%) | 110 (15%) | 25 (20%) | 161 (16%) | 123 (17%) | 24 (15%) | 14 (15%) | ||
CD274 (PD-L1) expression score | 0.092 | 0.039 | ||||||||
0 | 69 (10%) | 7 (7.3%) | 51 (10%) | 11 (14%) | 69 (10%) | 39 (7.8%) | 18 (16%) | 12 (17%) | ||
1 | 195 (29%) | 30 (31%) | 139 (28%) | 26 (32%) | 195 (29%) | 140 (28%) | 37 (33%) | 18 (26%) | ||
2 | 192 (28%) | 36 (38%) | 131 (26%) | 25 (31%) | 192 (28%) | 142 (28%) | 28 (25%) | 22 (31%) | ||
3 | 192 (28%) | 18 (19%) | 158 (31%) | 16 (20%) | 192 (28%) | 153 (31%) | 24 (22%) | 15 (21%) | ||
4 | 33 (4.9%) | 5 (5.2%) | 25 (5.0%) | 3 (3.7%) | 33 (4.9%) | 26 (5.2%) | 4 (3.6%) | 3 (4.3%) | ||
PTGS2 (cyclooxygenase-2) expression | 0.028 | 0.016 | ||||||||
Negative | 377 (38%) | 59 (44%) | 266 (36%) | 52 (47%) | 377 (38%) | 264 (36%) | 64 (43%) | 49 (49%) | ||
Positive | 613 (62%) | 76 (56%) | 478 (64%) | 59 (53%) | 613 (62%) | 477 (64%) | 84 (57%) | 52 (51%) | ||
Nuclear CTNNB1 (beta-catenin) expression | <0.0001 | <0.0001 | ||||||||
Negative | 938 (64%) | 124 (64%) | 669 (62%) | 145 (79%) | 938 (64%) | 663 (61%) | 165 (75%) | 110(75%) | ||
Positive | 524 (36%) | 69 (36%) | 416 (38%) | 39 (21%) | 523 (36%) | 432 (39%) | 54 (25%) | 37 (25%) | ||
Neoantigen load | <0.0001 | <0.0001 | ||||||||
Q1 (lowest) | 125 (25%) | 29 (34%) | 84 (24%) | 12 (16%) | 125 (25%) | 104 (29%) | 20 (22%) | 1 (1.8%) | ||
Q2 | 123 (24%) | 19 (22%) | 92 (27%) | 12 (16%) | 123 (24%) | 104 (29%) | 14 (15%) | 5 (8.8%) | ||
Q3 | 129 (26%) | 29 (34%) | 86 (25%) | 14 (19%) | 129 (26%) | 100 (28%) | 19 (20%) | 10 (18%) | ||
Q4 (highest) | 128 (25%) | 9 (10%) | 82 (24%) | 37 (49%) | 128 (25%) | 47 (13%) | 40 (43%) | 41 (72%) | ||
