Table 1. Differential clinicopathologic features of CIMP-H CRC according to MLH1 promoter methylation status (original study samples; n = 65).
| Variables | Case No. | MLH1-methylated (n = 33) | MLH1-unmethylated (n = 32) | P-value | |
|---|---|---|---|---|---|
| Agea | < 66 years | 27 | 5 (15%) | 22 (69%) | < 0.001 |
| ≥ 66 years | 38 | 28 (85%) | 10 (31%) | ||
| Sex | Male | 32 | 15 (45%) | 17 (53%) | 0.536 |
| Female | 33 | 18 (55%) | 15 (47%) | ||
| Tumor location | Proximal | 45 | 27 (82%) | 18 (56%) | 0.026 |
| Distal | 20 | 6 (18%) | 14 (44%) | ||
| Gross tumor type | Fungating | 39 | 20 (61%) | 19 (59%) | 0.919 |
| Infiltrative | 26 | 13 (39%) | 13 (41%) | ||
| AJCC TNM stage | Stage I/II | 20 | 12 (36%) | 8 (25%) | 0.321 |
| Stage III/IV | 45 | 21 (64%) | 24 (75%) | ||
| Depth of primary tumor invasion (pT category) | pT1/pT2 | 2 | 1 (3%) | 1 (3%) | 1 |
| pT3/pT4 | 63 | 32 (97%) | 31 (97%) | ||
| Lymph node metastasis (pN category) | Absent (pN0) | 20 | 12 (36%) | 8 (25%) | 0.321 |
| Present (pN1/pN2) | 45 | 21 (64%) | 24 (75%) | ||
| Distant metastasis (M category) | Absent (M0) | 50 | 29 (88%) | 21 (66%) | 0.033 |
| Present (M1) | 15 | 4 (12%) | 11 (34%) | ||
| Tumor differentiation | WD/MD | 48 | 23 (70%) | 25 (78%) | 0.44 |
| PD | 17 | 10 (30%) | 7 (22%) | ||
| Mucinous histology | Absent | 34 | 9 (27%) | 25 (78%) | < 0.001 |
| Present | 31 | 24 (73%) | 7 (22%) | ||
| Signet ring cell histology | Absent | 58 | 27 (82%) | 31 (97%) | 0.105 |
| Present | 7 | 6 (18%) | 1 (3%) | ||
| Medullary histology | Absent | 60 | 29 (88%) | 31 (97%) | 0.355 |
| Present | 5 | 4 (12%) | 1 (3%) | ||
| Serrated histology | Absent | 50 | 26 (79%) | 24 (75%) | 0.717 |
| Present | 15 | 7 (21%) | 8 (25%) | ||
| Lymphatic invasion | Absent | 22 | 12 (36%) | 10 (31%) | 0.663 |
| Present | 43 | 21 (64%) | 22 (69%) | ||
| Venous invasion | Absent | 55 | 32 (97%) | 23 (72%) | 0.006 |
| Present | 10 | 1 (3%) | 9 (28%) | ||
| Perineural invasion | Absent | 45 | 28 (85%) | 17 (53%) | 0.006 |
| Present | 20 | 5 (15%) | 15 (47%) | ||
| Tumor budding | Absent | 22 | 16 (48%) | 6 (19%) | 0.011 |
| Present | 43 | 17 (52%) | 26 (81%) | ||
| Tumor-infiltrating lymphocytes (TILs)b | Low-density (< 21 TILs/HPF) | 46 | 14 (42%) | 32 (100%) | < 0.001 |
| High-density (≥ 21 TILs/HPF) | 19 | 19 (58%) | 0 (0%) | ||
| Peritumoral lymphoid reactionb | Absent or mild | 42 | 15 (47%) | 27 (84%) | 0.002 |
| Moderate to marked | 22 | 17 (53%) | 5 (16%) | ||
| Crohn-like lymphoid reaction (Ueno criteria)c | Inactive (largest LA < 1 mm) | 51 | 21 (66%) | 30 (94%) | 0.005 |
| Active (largest LA ≥ 1 mm) | 13 | 11 (34%) | 2 (6%) | ||
| Crohn-like lymphoid reaction (Väyrynen-Mäkinen criteria)c | Low-density (< 0.38/mm) | 29 | 10 (31%) | 19 (59%) | 0.024 |
| High-density (≥ 0.38/mm) | 35 | 22 (69%) | 13 (41%) |
Abbreviations: CIMP-H, CpG island methylator phenotype-high; AJCC, American Joint Committee on Cancer; TNM, tumor-node-metastasis; WD, well differentiated; MD, moderately differentiated; PD, poorly differentiated; HPF, high power field; LA, lymphoid aggregate.
a
Dichotomous age groups were classified using a cutoff value of the average age (66 years).
b
Dichotomous TIL groups were classified using a cutoff value of the average TIL density (21/HPF).
c
Peritumoral lymphoid reaction and Crohn-like lymphoid reaction were assessed in 64 out of the 65 CIMP-H CRCs due to the inadequate quality of tissue sections for lymphoid reaction evaluations in one case.