Table 1.
Clinical, pathologic and molecular features according to lymphocytic reactions to colorectal cancer
| Clinical or molecular feature | All cases | Overall lymphocytic reaction score | P value | ||
|---|---|---|---|---|---|
| 0-2 | 3-6 | 7-12 | |||
| Total N | 843 | 549 | 230 | 64 | |
| Sex | 0.32 | ||||
| Male (HPFS) | 361 (43%) | 240 (44%) | 90 (39%) | 31 (48%) | |
| Female (NHS) | 482 (57%) | 309 (56%) | 140 (61%) | 33 (52%) | |
| Mean age (years) ± SD | 66.3 ± 8.3 | 65.8 ± 8.4 | 66.8 ± 8.1 | 69.1 ± 7.8 | 0.002 |
| Body mass index (BMI) | 0.56 | ||||
| <30 kg/m2 | 663 (84%) | 425 (83%) | 185 (85%) | 53 (87%) | |
| ≥30 kg/m2 | 131 (16%) | 90 (17%) | 33 (15%) | 8 (13%) | |
| Family history of colorectal cancer in 1st degree relative(s) | 0.75 | ||||
| (-) | 637 (76%) | 411 (75%) | 178 (77%) | 48 (75%) | |
| (+) | 206 (24%) | 138 (25%) | 52 (23%) | 16 (25%) | |
| Year of diagnosis | 0.20 | ||||
| Prior to 1990 | 148 (18%) | 105 (19%) | 37 (16%) | 6 (9.4%) | |
| 1990 to 1999 | 598 (71%) | 381 (69%) | 164 (71%) | 53 (83%) | |
| 2000 to 2002 | 97 (12%) | 63 (11%) | 29 (13%) | 5 (7.8%) | |
| Tumor location | <0.0001 | ||||
| Proximal (cecum to transverse) | 381 (45%) | 206 (38%) | 131 (57%) | 44 (69%) | |
| Distal colon (splenic flexure to sigmoid) | 267 (32%) | 185 (34%) | 65 (28%) | 17 (27%) | |
| Rectum | 195 (23%) | 158 (29%) | 34 (15%) | 3 (4.7%) | |
| AJCC tumor stage | 0.002 | ||||
| I | 187 (22%) | 129 (24%) | 44 (19%) | 14 (22%) | |
| II | 242 (29%) | 139 (25%) | 76 (33%) | 27 (42%) | |
| III | 242 (29%) | 150 (27%) | 74 (32%) | 18 (28%) | |
| IV | 118 (14%) | 95 (17%) | 21 (9.1%) | 2 (3.1%) | |
| Unknown | 54 (6.4%) | 36 (6.6%) | 15 (6.5%) | 3 (4.7%) | |
| No. of lymph nodes examined | 0.0007 | ||||
| 0-3 | 80 (12%) | 62 (14%) | 14 (7.3%) | 4 (7.1%) | |
| 4-6 | 105 (15%) | 76 (17%) | 24 (13%) | 5 (8.9%) | |
| 7-12 | 245 (36%) | 162 (37%) | 67 (35%) | 16 (29%) | |
| ≥13 | 256 (37%) | 138 (32%) | 87 (45%) | 31 (55%) | |
| No. of negative lymph nodes | <0.0001 | ||||
| 0-3 | 131 (19%) | 99 (23%) | 27 (14%) | 5 (8.9%) | |
| 4-6 | 125 (18%) | 92 (21%) | 25 (13%) | 8 (14%) | |
| 7-12 | 223 (33%) | 138 (32%) | 70 (36%) | 15 (27%) | |
| ≥13 | 207 (30%) | 109 (25%) | 70 (36%) | 28 (50%) | |
| Tumor grade | <0.0001 | ||||
| Low | 755 (90%) | 515 (95%) | 200 (87%) | 40 (63%) | |
| High | 82 (9.8%) | 28 (5.2%) | 30 (13%) | 24 (37%) | |
| MSI | <0.0001 | ||||
| MSI-low/MSS | 702 (85%) | 503 (94%) | 169 (74%) | 30 (47%) | |
| MSI-high | 124 (15%) | 31 (5.8%) | 59 (26%) | 34 (53%) | |
| CIMP | <0.0001 | ||||
| CIMP-low/0 | 685 (84%) | 488 (93%) | 165 (73%) | 32 (50%) | |
| CIMP-high | 127 (16%) | 34 (6.5%) | 61 (27%) | 32 (50%) | |
| Mean LINE-1 methylation (%) ± SD | 61.2 ± 9.4 | 60.4 ± 9.5 | 62.3 ± 8.6 | 63.8 ± 10.7 | 0.001 |
| BRAF mutation | <0.0001 | ||||
| (-) | 699 (86%) | 479 (91%) | 178 (81%) | 42 (68%) | |
| (+) | 112 (14%) | 49 (9.3%) | 43 (19%) | 30 (32%) | |
| KRAS mutation | 0.11 | ||||
| (-) | 528 (63%) | 346 (64%) | 135 (59%) | 47 (73%) | |
| (+) | 304 (37%) | 195 (36%) | 92 (41%) | 17 (27%) | |
| p53 expression | <0.0001 | ||||
| (-) | 471 (57%) | 271 (50%) | 150 (66%) | 50 (78%) | |
| (+) | 358 (43%) | 267 (50%) | 77 (34%) | 14 (22%) | |
| COX-2 expression | 0.015 | ||||
| (-) | 136 (16%) | 74 (14%) | 50 (22%) | 12 (19%) | |
| (+) | 701 (84%) | 470 (86%) | 179 (78%) | 52 (81%) | |
(%) indicates the proportion of tumors with a specific clinical, pathologic or molecular feature in all patients or patients with a specific category of lymphocytic reactions.
*
Overall lymphocytic reaction score is the sum of scores for Crohn's-like reaction (0-3), peritumoral reaction (0-3), intratumoral periglandular reaction (0-3), and tumor infiltrating lymphocytes (TIL, 0-3).
CIMP, CpG island methylator phenotype; HPFS, Health Professionals Follow-up Study; LINE-1, long interspersed nucleotide element-1; MSI, microsatellite instability; MSS, microsatellite stable; NHS, Nurses' Health Study; SD, standard deviation.