Background
Methods
Study group
Tissue microarray construction
Immunohistochemistry and staining evaluation
Statistical analysis
Results
Associations of MSI screening status and beta-catenin overexpression with clinicopathological characteristics and investigative factors
MSI screening status | Beta-catenin score | ||||||
---|---|---|---|---|---|---|---|
n (%) | MSS | MSI | P-value | 0-1 | 2-3 | 4-5 | P-value |
438(85.0) | 77(15.0) | 159(30.2) | 170(32.3) | 198(37.6) | |||
Age
| |||||||
<=75 | 308(70.3) | 41(53.2) | 0.003* | 101(63.5) | 123(72.4) | 133(67.2) | 0.561 |
>75 | 130(29.7) | 36(46.8) | 58(36.5) | 47(27.6) | 65(32.8) | ||
Sex
| |||||||
Female | 222(50.7) | 50(64.9) | 0.021* | 87(54.7) | 90(52.9) | 100(50.5) | 0.425 |
Male | 216(49.3) | 27(35.1) | 72(45.3) | 80(47.1) | 98(49.5) | ||
Tumour location
| |||||||
Proximal | 107(24.5) | 62(80.5) | <0.001** | 84(53.2) | 50(29.4) | 37(18.8) | <0.001** |
Transverse | 12(2.8) | 8(10.4) | 11(7.0) | 7(4.1) | 5(2.5) | ||
Descending | 26(6.0) | 1(1.3) | 6(3.8) | 11(6.5) | 9(4.6) | ||
Sigmoid | 105(24.1) | 3(3.9) | 19(12.0) | 31(18.2) | 60(30.5) | ||
Rectum | 186(42.7) | 3(3.9) | 38(24.1) | 71(41.8) | 86(43.7) | ||
Unknown | 2 | 0 | 1 | 0 | 1 | ||
T stage
| |||||||
1 | 45(10.8) | 3(3.9) | 0.116 | 12(8.0) | 11(6.9) | 23(11.9) | 0.039* |
2 | 53(12.7) | 7(9.2) | 14(9.3) | 21(13.1) | 27(14.0) | ||
3 | 257(61.5) | 54(71.1) | 99(66.0) | 100(62.5) | 119(61.7) | ||
4 | 63(15.1) | 12(15.8) | 25(16.7) | 28(17.5) | 24(12.4) | ||
missing | 20 | 1 | 9 | 10 | 5 | ||
N stage
| |||||||
0 | 222(56.5) | 54(72.0) | 0.017* | 84(57.5) | 86(55.8) | 109(60.9) | 0.249 |
1 | 101(25.7) | 12(16.0) | 28(19.2) | 44(28.6) | 44(24.6) | ||
2 | 70(17.8) | 9(12.0) | 34(23.3) | 24(15.6) | 26(14.5) | ||
missing | 45 | 2 | 13 | 16 | 19 | ||
M stage
| |||||||
0 | 352(81.7) | 72(93.5) | 0.010* | 123(78.8) | 140(83.3) | 166(85.1) | 0.131 |
1 | 79(18.3) | 5(6.5) | 33(21.2) | 28(16.7) | 29(14.9) | ||
missing | 7 | 0 | 3 | 2 | 3 | ||
Differentiation grade
| |||||||
High | 28(6.5) | 6(8.0) | 0.003** | 16(10.3) | 8(4.8) | 10(5.1) | 0.016* |
Intermediate | 321(74.5) | 40(53.3) | 94(60.3) | 115(69.3) | 159(81.5) | ||
Low | 82(19.0) | 29(38.7) | 46(29.5) | 43(25.9) | 26(13.3) | ||
missing | 7 | 2 | 3 | 4 | 4 | ||
Vascular invasion
| |||||||
No | 121(47.8) | 26(57.8) | 0.220 | 48(50.5) | 33(36.3) | 68(58.1) | 0.177 |
Yes | 132(52.2) | 19(42.2) | 47(49.5) | 58(63.7) | 49(41.9) | ||
missing | 185 | 32 | 64 | 79 | 81 |
MSI screening status | Beta-catenin score | ||||||
---|---|---|---|---|---|---|---|
n (%) | MSS | MSI | P-value | 0-1 | 2-3 | 4-5 | P-value |
438(85.0) | 77(15.0) | 159(30.2) | 170(32.3) | 198(37.6) | |||
P53 status
| |||||||
Negative | 196(40.0) | 62(80.5) | <0.001** | 101(65.2) | 92(55.1) | 76(38.6) | <0.001** |
Positive | 230(54.0) | 15(19.5) | 54(34.8) | 75(44.9) | 121(61.4) | ||
missing | 12 | 0 | 4 | 3 | 1 | ||
Cyclin D1 fraction
| |||||||
0-1% | 94(22.1) | 2(2.6) | <0.001** | 36(23.4) | 36(21.7) | 31(15.8) | 0.001** |
2-25% | 159(37.4) | 26(34.2) | 63(40.9) | 65(39.2) | 63(32.1) | ||
26-50% | 65(15.3) | 16(21.1) | 20(13.0) | 29(17.5) | 33(16.8) | ||
51-75% | 87(20.5) | 25(32.9) | 27(17.5) | 32(19.3) | 53(27.0) | ||
>75% | 20(4.7) | 7(9.2) | 8(5.2) | 4(2.4) | 16(8.2) | ||
missing | 13 | 1 | 5 | 4 | 2 | ||
Cyclin D1 intensity
| |||||||
Negative | 94(22.1) | 2(2.6) | <0.001** | 36(23.4) | 36(21.7) | 31(15.8) | 0.085 |
Weak | 154(36.2) | 20(26.3) | 51(33.1) | 59(35.5) | 68(34.7) | ||
Moderate | 129(30.4) | 41(53.9) | 49(31.8) | 55(33.1) | 68(34.7) | ||
Strong | 48(11.3) | 13(17.1) | 18(11.7) | 16(9.6) | 29(14.8) | ||
missing | 13 | 1 | 5 | 4 | 2 | ||
P27 fraction
| |||||||
0-1% | 54(12.7) | 24(31.2) | 0.003** | 43(27.9) | 33(19.8) | 8(4.1) | <0.001** |
2-25% | 96(22.6) | 14(18.2) | 36(23.4) | 43(25.7) | 35(17.9) | ||
26-50% | 90(21.2) | 16(20.8) | 32(20.8) | 40(24.0) | 36(18.4) | ||
51-75% | 134(31.5) | 15(19.5) | 31(20.1) | 36(21.6) | 83(42.3) | ||
>75% | 51(12.0) | 8(10.4) | 12(7.8) | 15(9.0) | 34(17.3) | ||
missing | 13 | 1 | 5 | 3 | 2 | ||
P27 intensity
| |||||||
Negative | 54(12.7) | 24(31.2) | <0.001** | 43/27.9) | 33(19.8) | 8(4.1) | <0.001** |
Weak | 96(22.6) | 22(28.6) | 46(29.9) | 39(23.4) | 37(18.9) | ||
Moderate | 142(33.4) | 18(23.4) | 50(32.5) | 51(30.5) | 62(31.6) | ||
Strong | 133(31.3) | 13(16.9) | 15(9.7) | 44(26.3) | 89(45.4) | ||
missing | 13 | 1 | 5 | 3 | 2 | ||
P21 fraction
| |||||||
0-1% | 69(16.3) | 3(3.9) | 0.002** | 25(16.2) | 27(16.2) | 25(12.9) | 0.835 |
2-25% | 233(55.1) | 41(53.2) | 81(52.6) | 90(53.9) | 112857.7) | ||
26-50% | 60(14.2) | 18(23.4) | 24(15.6) | 28(16.8) | 26(13.4) | ||
51-75% | 53(12.5) | 13(16.9) | 21(13.6) | 16(9.6) | 30(15.5) | ||
>75% | 8(1.9) | 2(2.6) | 3(1.9) | 6(3.6) | 1(0.5= | ||
missing | 15 | 1 | 5 | 3 | 4 | ||
P21 intensity
| |||||||
Negative | 69(16.3) | 3(3.9) | <0.001** | 25(16.2) | 27(16.2) | 25(12.9) | 0.567 |
Weak | 174(41.1) | 24(31.2) | 60(39.0) | 63(37.7) | 81(41.8) | ||
Moderate | 122(28.8) | 36(46.8) | 51(33.1) | 52(31.1) | 60(30.9) | ||
Strong | 58(13.7) | 14(18.2) | 18(11.7) | 25(15.0) | 28(14.4) | ||
missing | 15 | 1 | 5 | 3 | 4 | ||
MSI screening status
| |||||||
MSS | - | - | 109(72.7) | 136(83.4) | 184(95.8) | <0.001** | |
MSI | - | - | 41(27.3) | 27(16.6) | 8(4.2) | ||
missing | 9 | 7 | 6 |
Association of MSI screening status and beta-catenin overexpression with survival
Full cohort | Stage III-IV disease | |||||
---|---|---|---|---|---|---|
HR(95% CI) |
p-value
|
N(events)
| HR(95% CI) |
p-value
|
n(events)
| |
Univariable
|
Univariable
| |||||
MSS | 1,00 | 0,010** | 438(157) | 1,00 | 0,036* | 201(122) |
MSI | 0,50(0,29-0,84) | 77(15) | 0,46(0,23-0,95) | 23(8) | ||
Multivariable
|
Multivariable
| |||||
MSS | 1,00 | 0,010* | 389(137) | 1,00 | 0,011* | 185(107) |
MSI | 0,46(0,25-0,84) | 73(13) | 0,33(0,14-0,78) | 20(6) | ||
Univariable
|
Univariable
| |||||
Bata-catenin low | 1,00 | 0,056 | 251(96) | 1,00 | 0,063 | 112(72) |
Bata-catenin High | 0,75(0,56-1,01) | 276(86) | 0,73(0,52-1,02) | 122(66) | ||
Multivariable
|
Multivariable
| |||||
Bata-catenin low | 1,00 | 0,031* | 223(80) | 1,00 | 0,036* | 98(60) |
Bata-catenin High | 0,70(0,51-0,97) | 247(75) | 0,67(0,46-0,97) | 113(57) |