Table 1.

Clinical and molecular characteristics of CRC cases according to combined CIMP and MSI screening status

A. NSHDS cases
Total*MSSPMSIP
CIMP-negative§CIMP-low§CIMP-high§CIMP-negative§CIMP-low§CIMP-high§
Frequency (%)19091 (47.9)61 (32.1)14 (7.4)4 (2.1)7 (3.7)13 (6.8)
Age at diagnosis (y)63 (58-67)63 (57-67)63 (59-66)65 (63-68)0.21958 (57-60)68 (59-69)63 (61-68)0.105
Sex, n (%)
    Men82 (43.2)42 (46.2)26 (42.6)5 (35.7)4 (100.0)4 (57.1)1 (7.7)
    Women108 (56.8)49 (53.8)35 (57.4)9 (64.3)0.7380 (0.0)3 (42.9)12 (92.3)<0.001
Tumor site, n (%)
    Right-sided colon61 (32.1)15 (16.5)19 (31.1)8 (57.1)2 (50.0)4 (57.1)13 (100.0)
    Left-sided colon56 (29.5)29 (31.9)22 (36.1)2 (14.3)1 (25.0)2 (28.6)0 (0.0)
    Rectum73 (38.4)47 (51.6)20 (32.8)4 (28.6)0.0071 (25.0)1 (14.3)0 (0.0)0.023
Stage, n (%)
    I33 (17.4)23 (25.3)6 (9.8)2 (14.3)0 (0.0)1 (14.3)1 (7.7)
    II68 (35.8)29 (31.9)21 (34.4)3 (21.4)3 (75.0)3 (42.9)9 (69.2)
    III46 (24.2)25 (27.5)16 (26.2)1 (7.1)1 (25.0)0 (0.0)3 (23.1)
    IV43 (22.6)14 (15.4)18 (29.5)8 (57.1)0.0100 (0.0)3 (42.9)0 (0.0)0.108
Tumor grade
    Well to moderately differentiated
    Moderately to poorly differentiated
Histology type, n (%)
    Nonmucinous151 (79.9)83 (91.2)46 (76.7)10 (71.4)3 (75.0)2 (28.6)7 (53.8)
    Mucinous38 (20.1)8 (8.8)14 (23.3)4 (28.6)0.0141 (25.0)5 (71.4)6 (46.2)0.303
BRAF V600E, n (%)
    Wild-type154 (81.5)87 (96.7)50 (82.0)4 (28.6)4 (100.0)5 (71.4)4 (30.8)
    Mutated35 (18.5)3 (3.3)11 (18.0)10 (71.4)<0.0010 (0.0)2 (28.6)9 (69.2)0.032
p53 screening status
    Normal75 (40.1)33 (36.7)20 (33.3)7 (50.0)4 (100.0)2 (28.6)9 (75.0)
    Aberrant112 (59.9)57 (63.3)40 (66.7)7 (50.0)0.5070 (0.0)5 (71.4)3 (25.0)0.040
Adjuvant chemotherapy
    No147 (82.1)72 (82.8)48 (82.8)12 (85.7)3 (100.0)5 (71.4)7 (70.0)
    Yes32 (17.9)15 (17.2)10 (17.2)2 (14.3)1.0000 (0.0)2 (28.6)3 (30.0)0.817
Preoperative radiotherapy**
    No26 (35.6)16 (34.0)9 (45.0)1 (25.0)0 (0.0)0 (0.0)0 (0.0)
    Yes47 (64.4)31 (66.0)11 (55.0)3 (75.0)0.5831 (100.0)1 (100.0)0 (0.0)
B. CRUMS cases
Total††MSSPMSIP
CIMP-negative§CIMP-low§CIMP-high§CIMP-negative§CIMP-low§CIMP-high§
Frequency (%)414194 (48.5)132 (33.0)12 (3.0)12 (3.0)15 (3.8)35 (8.8)
Age at diagnosis (y)73 (65-79)72 (64-79)73 (66-81)74 (69-78)0.64472 (61-77)75 (61-83)73 (69-77)0.728
Sex, n (%)
    Men233 (56.3)113 (58.2)79 (59.8)3 (25.0)5 (41.7)7 (46.7)19 (54.3)
    Women181 (43.7)81 (41.8)53 (40.2)9 (75.0)0.0677 (58.3)8 (53.3)16 (45.7)0.720
Tumor site, n (%)
    Right-sided colon132 (32.0)26 (13.5)46 (34.8)9 (75.0)4 (33.3)10 (66.7)32 (91.4)
    Left-sided colon127 (30.8)79 (41.1)37 (28.0)2 (16.7)2 (16.7)3 (20.0)2 (5.7)
    Rectum153 (37.1)87 (45.3)49 (37.1)1 (8.3)<0.0016 (50.0)2 (13.3)1 (2.9)<0.001
Stage, n (%)
    I63 (15.5)38 (19.8)15 (11.7)0 (0.0)1 (8.3)2 (13.3)4 (11.4)
    II163 (40.0)72 (37.5)52 (40.6)2 (16.7)6 (50.0)6 (40.0)20 (57.1)
    III88 (21.6)38 (19.8)30 (23.4)5 (41.7)2 (16.7)5 (33.3)6 (17.1)
    IV93 (22.9)44 (22.9)31 (24.2)5 (41.7)0.0833 (25.0)2 (13.3)5 (14.3)0.825
Tumor grade
    Well to moderately differentiated203 (49.6)102 (53.1)56 (43.4)7 (58.3)10 (83.3)6 (40.0)14 (40.0)
    Moderately to poorly differentiated206 (50.4)90 (46.9)73 (56.6)5 (41.7)0.1922 (16.7)9 (60.0)21 (60.0)0.024
Histology type, n (%)
    Nonmucinous347 (85.0)175 (91.1)111 (86.0)8 (66.7)8 (72.7)12 (80.0)22 (62.9)
    Mucinous61 (15.0)17 (8.9)18 (14.0)4 (33.3)0.0273 (27.3)3 (20.0)13 (37.1)0.486
BRAF V600E, n (%)
    Wild-type356 (86.6)190 (98.4)123 (93.9)4 (33.3)12 (100.0)12 (80.0)3 (8.8)
    Mutated55 (13.4)3 (1.6)8 (6.1)8 (66.7)<0.0010 (0.0)3 (20.0)31 (91.2)<0.001
p53 screening status
    Normal161 (39.7)68 (35.6)44 (34.1)7 (58.3)6 (50.0)6 (40.0)22 (66.7)
    Aberrant245 (60.3)123 (64.4)85 (65.9)5 (41.7)0.2526 (50.0)9 (60.0)11 (33.3)0.196
Adjuvant chemotherapy
    No358 (87.5)172 (88.7)113 (88.3)10 (83.3)10 (83.3)11 (73.3)30 (85.7)
    Yes51 (12.5)22 (11.3)15 (11.7)2 (16.7)0.7752 (16.7)4 (26.7)5 (14.3)0.544
Preoperative radiotherapy**
    No67 (43.8)35 (40.2)23 (46.9)0 (0.0)2 (33.3)1 (50.0)0 (0.0)
    Yes86 (56.2)52 (59.8)26 (53.1)1 (100.0)0.6974 (66.7)1 (50.0)1 (100.0)1.000
  • *The following numbers of missing cases were present in NSHDS: tumor grade, all; mucinous histologic type, 1; BRAF mutation status, 1; p53 screening status, 3; adjuvant chemotherapy, 11.

  • Cases lacking nuclear staining of tumor cells for at least one of MLH1, MSH2, MSH6, or PMS2 were considered to have a positive MSI screening status.

  • Kruskall-Wallis test for continuous variables and χ2 test or Fisher's exact test for categorical variables.

  • §CIMP-negative, 0 genes hypermethylated; CIMP-low, 1 to 5 genes hypermethylated; CIMP-high, 6 to 8 genes hypermethylated.

  • Median (25th-75th percentile).

  • Cases were considered to have overexpression of p53 if ≥25% of tumor cells (by semiquantitative assessment) showed nuclear staining for p53 protein.

  • **Only rectal cancers were considered. The percentages presented therefore reflect the proportion of rectal cancer cases that received preoperative radiotherapy.

  • ††The following numbers of missing cases were present in CRUMS: MSI screening status, 14; tumor site, 2; tumor stage, 7; tumor grade, 5; mucinous histologic type, 6; BRAF mutation status, 3; p53 screening status, 8; adjuvant chemotherapy, 5.