Clinicopathological and molecular characteristics according to CLR status determined by the three assessment criteria in MSI-H CRCs (n=212)
| Ueno criteria | Väyrynen–Mäkinen criteria | Graham–Appelman criteria | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Characteristics | Total cases | Active CLR (≥1 mm) cases (%) | Inactive CLR (<1 mm) cases (%) | p Value | High-density CLR (≥0.38 LAs/mm) cases (%) | Low-density CLR (<0.38 LAs/mm) cases (%) | p Value | Intense CLR (grade 2) cases (%) | No or mild CLR (grade 0/1) cases (%) | p Value |
| Age (years) | ||||||||||
| <58 | 101 | 43 (50) | 58 (46) | 0.57 | 66 (48) | 35 (47) | 0.941 | 22 (46) | 79 (48) | 0.776 |
| ≥58 | 111 | 43 (50) | 68 (54) | 72 (52) | 39 (53) | 26 (54) | 85 (52) | |||
| Gender | ||||||||||
| Male | 112 | 43 (50) | 57 (45) | 0.495 | 77 (56) | 35 (47) | 0.237 | 30 (63) | 82 (50) | 0.127 |
| Female | 100 | 43 (50) | 69 (55) | 61 (44) | 39 (53) | 18 (38) | 82 (50) | |||
| Tumour location | ||||||||||
| Proximal | 137 | 59 (69) | 78 (62) | 0.316 | 93 (67) | 44 (59) | 0.25 | 36 (75) | 101 (62) | 0.087 |
| Distal | 75 | 27 (31) | 48 (38) | 45 (33) | 30 (41) | 12 (25) | 63 (38) | |||
| AJCC/UICC TNM stage | ||||||||||
| Stage I/II | 138 | 64 (74) | 74 (59) | 0.019 | 97 (70) | 41 (55) | 0.03 | 37 (77) | 101 (62) | 0.048 |
| Stage III/IV | 74 | 22 (26) | 52 (41) | 41 (30) | 33 (45) | 11 (23) | 63 (38) | |||
| WHO tumour grade | ||||||||||
| G1/G2 | 170 | 71 (83) | 99 (79) | 0.475 | 117 (85) | 53 (72) | 0.022 | 39 (81) | 131 (80) | 0.834 |
| G3 | 42 | 15 (17) | 27 (21) | 21 (15) | 21 (28) | 9 (19) | 33 (20) | |||
| Mucinous component | ||||||||||
| Absent | 90 | 36 (42) | 54 (43) | 0.885 | 60 (43) | 30 (41) | 0.68 | 24 (50) | 66 (40) | 0.229 |
| Present | 122 | 50 (58) | 72 (57) | 78 (57) | 44 (59) | 24 (50) | 98 (60) | |||
| Medullary component | ||||||||||
| Absent | 205 | 82 (95) | 123 (98) | 0.445 | 133 (96) | 72 (97) | 1 | 47 (98) | 158 (96) | 1 |
| Present | 7 | 4 (5) | 3 (2) | 5 (4) | 2 (3) | 1 (2) | 6 (4) | |||
| Signet ring cell component | ||||||||||
| Absent | 192 | 79 (92) | 113 (90) | 0.594 | 124 (90) | 68 (92) | 0.629 | 45 (94) | 147 (90) | 0.576 |
| Present | 20 | 7 (8) | 13 (10) | 14 (10) | 6 (8) | 3 (6) | 17 (10) | |||
| Tumour border | ||||||||||
| Expanding | 34 | 16 (19) | 18 (14) | 0.4 | 24 (17) | 10 (14) | 0.463 | 11 (23) | 23 (14) | 0.14 |
| Infiltrative | 178 | 70 (81) | 108 (86) | 114 (83) | 64 (86) | 37 (77) | 141 (86) | |||
| Tumour budding | ||||||||||
| Negative | 168 | 75 (87) | 93 (74) | 0.018 | 112 (81) | 56 (76) | 0.348 | 39 (81) | 129 (79) | 0.697 |
| Positive | 44 | 11 (13) | 33 (26) | 26 (19) | 18 (24) | 9 (19) | 35 (21) | |||
| Lymphovascular invasion | ||||||||||
| Absent | 157 | 72 (84) | 85 (67) | 0.008 | 108 (78) | 49 (66) | 0.057 | 39 (81) | 118 (72) | 0.196 |
| Present | 55 | 14 (16) | 41 (33) | 30 (22) | 25 (34) | 9 (19) | 46 (28) | |||
| Perineural invasion | ||||||||||
| Absent | 196 | 82 (95) | 114 (90) | 0.187 | 131 (95) | 65 (88) | 0.062 | 45 (94) | 151 (92) | 1 |
| Present | 16 | 4 (5) | 12 (10) | 7 (5) | 9 (12) | 3 (6) | 13 (8) | |||
| MLH1 expression | ||||||||||
| Loss | 134 | 57 (66) | 77 (61) | 0.444 | 89 (64) | 45 (61) | 0.596 | 32 (67) | 102 (62) | 0.572 |
| Retained | 78 | 29 (34) | 49 (39) | 49 (36) | 29 (39) | 16 (33) | 62 (38) | |||
| MSH2 expression | ||||||||||
| Loss | 66 | 26 (30) | 40 (32) | 0.815 | 41 (30) | 25 (34) | 0.541 | 12 (25) | 54 (33) | 0.297 |
| Retained | 146 | 60 (70) | 86 (68) | 97 (70) | 49 (66) | 36 (75) | 110 (67) | |||
| PMS2 expression | ||||||||||
| Loss | 141 | 60 (70) | 81 (64) | 0.406 | 94 (68) | 47 (64) | 0.499 | 35 (73) | 106 (65) | 0.285 |
| Retained | 71 | 26 (30) | 45 (36) | 44 (32) | 27 (36) | 13 (27) | 58 (35) | |||
| MSH6 expression | ||||||||||
| Loss | 73 | 27 (31) | 46 (37) | 0.442 | 44 (32) | 29 (39) | 0.286 | 13 (27) | 60 (37) | 0.223 |
| Retained | 139 | 59 (69) | 80 (63) | 94 (68) | 45 (61) | 35 (73) | 104 (63) | |||
| KRAS mutation | ||||||||||
| Wild type | 163 | 68 (81) | 95 (79) | 0.67 | 103 (77) | 60 (83) | 0.319 | 33 (72) | 130 (82) | 0.138 |
| Mutant | 42 | 16 (19) | 26 (21) | 30 (23) | 12 (17) | 13 (28) | 29 (18) | |||
| BRAF mutation | ||||||||||
| Wild type | 188 | 77 (90) | 111 (88) | 0.745 | 124 (90) | 64 (86) | 0.461 | 43 (90) | 145 (88) | 0.822 |
| Mutant | 24 | 9 (10) | 15 (12) | 14 (10) | 10 (14) | 5 (10) | 19 (12) | |||
| CIMP status | ||||||||||
| CIMP-H | 54 | 19 (22) | 35 (28) | 0.351 | 31 (22) | 23 (31) | 0.17 | 8 (17) | 46 (28) | 0.111 |
| CIMP-L/0 | 158 | 67 (78) | 91 (72) | 107 (78) | 51 (69) | 40 (83) | 118 (72) | |||
CLR, Crohn-like lymphoid reaction; MSI-H, microsatellite instability-high; CRC, colorectal cancer; CIMP, CpG island methylator phenotype; CIMP-H, CIMP-high; CIMP-L/0, CIMP-low or CIMP-negative; LA, lymphoid aggregate; AJCC/UICC, American Joint Committee on Cancer/Union for International Cancer Control.