Table 1.
Clinicopathological and molecular characteristics of the two series.
| Norwegian series 1 (1993–2003) | Norwegian series 2 (2003–2012) | p value | ||
|---|---|---|---|---|
| Total patients, n | 922 | 798 | ||
| Age | Median (range) | 73 (29–94) | 72 (27–97) | 0.60 |
| Sex | Female | 485 (53%) | 407 (51%) | 0.53 |
| Male | 437 (47%) | 391 (49%) | ||
| TNM stage | I | 137 (15%) | 167 (21%) | 0.007 |
| II | 381 (41%) | 288 (36%) | ||
| III | 242 (26%) | 214 (27%) | ||
| IV | 159 (17%) | 129 (16%) | ||
| NA | 3 | – | ||
| pT | 1 | 37 (4%) | 40 (5%) | 0.0007 |
| 2 | 127 (14%) | 165 (21%) | ||
| 3 | 662 (72%) | 515 (65%) | ||
| 4 | 96 (10%) | 72 (9%) | ||
| NA | 0 | 6 | ||
| pN | 0 | 563 (62%) | 491 (62%) | 0.0008 |
| 1 | 250 (27%) | 175 (22%) | ||
| 2 | 99 (11%) | 129 (16%) | ||
| NA | 10 | 3 | ||
| Residual tumor (R) status | R0 | 719 (78%) | 651 (82%) | 0.09 |
| R1 | 36 (4%) | 19 (2%) | ||
| R2 | 167 (18%) | 128 (16%) | ||
| Tumor location | Right colon | 365 (40%) | 327 (41%) | 0.29 |
| Left colon | 301 (33%) | 239 (30%) | ||
| Rectum | 231 (25%) | 218 (27%) | ||
| Synchronous | 25 (3%) | 14 (2%) | ||
| MSI status | MSI | 128 (15%) | 120 (16%) | 0.78 |
| MSS | 712 (85%) | 638 (84%) | ||
| NA | 82 | 40 | ||
| BRAFV6ooE mutational status | Wild-type | 714 (85%) | 637 (84%) | 0.63 |
| Mutated | 127 (15%) | 122 (16%) | ||
| NA | 81 | 39 | ||
| KRAS mutational status | Wild-type | 463 (69%) | 238 (69%) | 0.94 |
| Mutated | 204 (31%) | 106 (31%) | ||
| NA | 255 | 454 | ||
| Adjuvant chemotherapy | No | 806 (87%) | 609 (79%) | <0.0001b |
| Yes | 116 (13%) | 162 (21%) | ||
| NA | 0 | 27 | ||
| Total CD3+-cells per mm2 (log2)a | Median (Q1–Q3) | 8.8 (7.3–10.0) | 8.8 (7.3–9.9) | 0.46 |
| Total CD8+-cells per mm2 (log2)a | Median (Q1–Q3) | 6.1 (4.2–8.0) | 6.0 (4.3–7.5) | 0.41 |
| Total FOXP3+-cells per mm2 (log2)a | Median (Q1–Q3) | 5.9 (3.9–7.4) | 5.8 (4.4–7.1) | 0.76 |
| Total tp-Treg-cells per mm2 (log2)a | Median (Q1–Q3) | 3.8 (0–5.4) | 3.6 (1.9–5.0) | 0.82 |
p values were calculated to determine if there were any statistical differences between the two consecutive Norwegian series; Wilcoxon rank-sum test was used for age and the immune-cell scores, Fisher Exact test for sex, adjuvant chemotherapy, MSI-, BRAF- and KRAS-status and chi-squared test for TNM stage, pT, pN, residual tumor status and tumor location.
MSI microsatellite instable, MSS microsatellite stable, pN regional lymph node classification, pT primary tumor classification, TNM Tumor-node-metastasis, tp-Treg triple-positive Treg.
an(Norwegian series 1) = 757 and n(Norwegian series 2) = 687; including all samples that were not excluded due to technical reasons (Supplementary Fig. 1).
bNational guidelines for adjuvant treatment have changed over time, reflecting the increased proportion receiving such therapy in the Norwegian series 2. Adjuvant chemotherapy for stage III CRC was introduced in national guidelines in 1997.