Table 3. Differential features of CIMP-H CRC according to MLH1 silencing status (TCGA dataset; n = 36).
| Variables | Case No. | MLH1-silenced (n = 24) | MLH1-non-silenced (n = 12) | P-value | |
|---|---|---|---|---|---|
| Agea | < 76 years | 15 | 8 (33%) | 7 (58%) | 0.151 |
| ≥ 76 years | 21 | 16 (67%) | 5 (42%) | ||
| Sex | Male | 14 | 5 (21%) | 9 (75%) | 0.003 |
| Female | 22 | 19 (79%) | 3 (25%) | ||
| Tumor location | Proximal | 33 | 24 (100%) | 9 (75%) | 0.031 |
| Distal | 3 | 0 (0%) | 3 (25%) | ||
| AJCC TNM stageb | Stage I/II | 23 | 16 (70%) | 7 (58%) | 0.709 |
| Stage III/IV | 12 | 7 (30%) | 5 (42%) | ||
| Depth of primary tumor invasion (pT category)c | pT1/pT2 | 5 | 3 (16%) | 2 (18%) | 1 |
| pT3/pT4 | 25 | 16 (84%) | 9 (82%) | ||
| Lymph node metastasis (pN category) | Absent (pN0) | 24 | 17 (71%) | 7 (58%) | 0.479 |
| Present (pN1/pN2) | 12 | 7 (29%) | 5 (42%) | ||
| Distant metastasis (M category) | Absent (M0) | 34 | 24 (100%) | 10 (83%) | 0.105 |
| Present (M1) | 2 | 0 (0%) | 2 (17%) | ||
| Histologic subtyped | Non-mucinous | 22 | 13 (57%) | 9 (75%) | 0.463 |
| Mucinous | 13 | 10 (43%) | 3 (25%) | ||
| Lymphatic invasione | Absent | 17 | 13 (57%) | 4 (40%) | 0.465 |
| Present | 16 | 10 (43%) | 6 (60%) | ||
| Vascular invasionf | Absent | 22 | 14 (78%) | 8 (89%) | 0.636 |
| Present | 5 | 4 (22%) | 1 (11%) | ||
| MSI status | MSI-L/MSS | 12 | 1 (4%) | 11 (92%) | < 0.001 |
| MSI-H | 24 | 23 (96%) | 1 (8%) | ||
| Mutational phenotypeg | Non-hypermutated | 12 | 1 (5%) | 11 (92%) | < 0.001 |
| Hypermutated | 20 | 19 (95%) | 1 (8%) | ||
| KRAS mutationh | Mutant | 11 | 1 (5%) | 10 (83%) | < 0.001 |
| Wild type | 21 | 19 (95%) | 2 (17%) | ||
| BRAF mutationh | Mutant | 16 | 15 (75%) | 1 (8%) | < 0.001 |
| Wild type | 16 | 5 (25%) | 11 (92%) | ||
| PIK3CA mutationh | Mutant | 9 | 4 (20%) | 5 (42%) | 0.24 |
| Wild type | 23 | 16 (80%) | 7 (58%) | ||
| APC mutationh | Mutant | 14 | 4 (20%) | 10 (83%) | < 0.001 |
| Wild type | 18 | 16 (80%) | 2 (17%) | ||
| CTNNB1 mutationh | Mutant | 1 | 0 (0%) | 1 (8%) | 0.375 |
| Wild type | 31 | 20 (100%) | 11 (92%) | ||
| TP53 mutationh | Mutant | 7 | 3 (15%) | 4 (33%) | 0.379 |
| Wild type | 25 | 17 (85%) | 8 (67%) |
Abbreviations: CIMP-H, CpG island methylator phenotype-high; AJCC, American Joint Committee on Cancer; TNM, tumor-node-metastasis; MSI, microsatellite instability; MSI-L, MSI-low; MSI-H, MSI-high; MSS, microsatellite stable.
Dichotomous age groups were classified using a cutoff value of the average age (76 years).
AJCC TNM stage data were not available in one case among the 36 CIMP-H CRCs from the TCGA dataset.
Depth of primary tumor invasion (pT) data were not available in six cases among the 36 CIMP-H CRCs from the TCGA dataset.
Histologic subtype (mucinous adenocarcinoma) data were not available in one case among the 36 CIMP-H CRCs from the TCGA dataset.
Lymphatic invasion data were not available in three cases among the 36 CIMP-H CRCs from the TCGA dataset.
Vascular invasion data were not available in nine cases among the 36 CIMP-H CRCs from the TCGA dataset.
Mutation rate data were not available in four cases among the 36 CIMP-H CRCs from the TCGA dataset.
KRAS/BRAF/PIK3CA/APC/CTNNB1/TP53 mutations data were not available in four cases among the 36 CIMP-H CRCs from the TCGA dataset.