Table 1.
Clinical and Molecular Features of Non–MSI-High Colorectal Cancer According to 18q LOH Status
Clinical or Molecular Feature | Total |
18q LOH Negative |
18q LOH Positive |
P | |||
---|---|---|---|---|---|---|---|
No. | % | No. | % | No. | % | ||
Total No. of patients | 555 | 193 | 362 | ||||
Sex | .36 | ||||||
Male, HPFS | 244 | 44 | 90 | 47 | 154 | 43 | |
Female, NHS | 311 | 56 | 103 | 53 | 208 | 57 | |
Age, years | .27 | ||||||
Mean | 66.8 | 67.3 | 66.5 | ||||
SD | 8.3 | 8.4 | 8.2 | ||||
Body mass index, kg/m2 | .018 | ||||||
< 30 | 424 | 82 | 154 | 88 | 270 | 80 | |
≥ 30 | 90 | 18 | 21 | 12 | 69 | 20 | |
Family history of colorectal cancer in first-degree relative(s) | .55 | ||||||
No | 428 | 77 | 146 | 76 | 282 | 78 | |
Yes | 127 | 23 | 47 | 24 | 80 | 22 | |
Year of diagnosis | .42 | ||||||
Before 1995 | 223 | 40 | 82 | 42 | 141 | 39 | |
1995 to 2002 | 332 | 60 | 111 | 58 | 221 | 61 | |
Tumor location | .025 | ||||||
Proximal, cecum to transverse | 217 | 40 | 89 | 48 | 128 | 36 | |
Distal colon, splenic flexure to sigmoid | 178 | 33 | 50 | 27 | 128 | 36 | |
Rectum | 144 | 27 | 48 | 26 | 96 | 27 | |
AJCC tumor stage | .26 | ||||||
I | 131 | 24 | 43 | 22 | 88 | 24 | |
IIA | 122 | 22 | 42 | 22 | 80 | 22 | |
IIB | 13 | 2.3 | 7 | 3.6 | 6 | 1.7 | |
IIIA | 24 | 4.3 | 12 | 6.2 | 12 | 3.3 | |
IIIB | 75 | 14 | 19 | 9.8 | 56 | 15 | |
IIIC | 64 | 12 | 23 | 12 | 41 | 11 | |
IV | 84 | 15 | 29 | 15 | 55 | 15 | |
Unknown | 42 | 7.6 | 18 | 9.3 | 24 | 6.6 | |
Tumor grade | .0060 | ||||||
Low | 506 | 93 | 167 | 89 | 339 | 95 | |
High | 36 | 6.6 | 20 | 11 | 16 | 4.5 | |
MSI status | .80 | ||||||
MSS | 495 | 89 | 173 | 90 | 322 | 89 | |
MSI low | 60 | 11 | 20 | 10 | 40 | 11 | |
CIMP, No. of methylated CIMP markers | .095 | ||||||
CIMP 0 | 272 | 50 | 82 | 44 | 190 | 54 | |
CIMP low (1–5) | 233 | 43 | 90 | 48 | 143 | 41 | |
CIMP high (6–8) | 34 | 6.3 | 14 | 7.5 | 20 | 5.7 | |
LINE-1 methylation, % | .040 | ||||||
Mean | 60.7 | 61.9 | 60.1 | ||||
SD | 9.3 | 9.5 | 9.2 | ||||
BRAFmutation | .45 | ||||||
Negative | 497 | 91 | 170 | 90 | 327 | 92 | |
Positive | 48 | 8.8 | 19 | 10 | 29 | 8.2 | |
KRASmutation | .015 | ||||||
Negative | 330 | 60 | 101 | 53 | 229 | 63 | |
Positive | 224 | 40 | 91 | 47 | 133 | 37 | |
PIK3CA mutation | .11 | ||||||
Negative | 438 | 85 | 145 | 82 | 293 | 87 | |
Positive | 75 | 15 | 32 | 18 | 43 | 13 | |
p53 expression | .071 | ||||||
Negative | 292 | 53 | 110 | 59 | 182 | 51 | |
Positive | 254 | 47 | 77 | 41 | 177 | 49 | |
β-catenin activation* | .30 | ||||||
Inactive (score 0-1) | 207 | 43 | 75 | 46 | 132 | 41 | |
Active (score 2-5) | 277 | 57 | 88 | 54 | 189 | 59 | |
JC virus T antigen | .0004 | ||||||
Negative | 285 | 60 | 120 | 71 | 165 | 54 | |
Positive | 190 | 40 | 50 | 29 | 140 | 46 |
NOTE. Table indicates the proportion of tumors with a specific clinical, pathologic, or molecular feature in all patients or patients with 18q LOH-negative tumors or 18q LOH-positive tumors.
Abbreviations: MSI, microsatellite instability; LOH, loss of heterozygosity; HPFS, Health Professionals Follow-Up Study; NHS, Nurses' Health Study; SD, standard deviation; AJCC, American Joint Committee on Cancer; MSS, microsatellite stable; CIMP, CpG island methylator phenotype; JC, John Cunningham.
β-catenin was assessed by immunohistochemistry and activation score was calculated as previously described.33