SAKK Swiss Group for Clinical Cancer Research, Coordinating Center, Bern; SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Laboratory of Tumor Cell Biology School of Medicine, University of Crete, Heraklion, Greece; Center for Human Genetics O&N1, Katholieke Universiteit Leuven, Leuven, Belgium.
Ann Oncol. 2015 Jan;26(1):126-132. doi: 10.1093/annonc/mdu499. Epub 2014 Oct 30.
Although colon cancer (CC) with microsatellite instability (MSI) has a more favorable prognosis than microsatellite stable (MSS) CC, the impact varies according to clinicopathological parameters. We studied how MSI status affects prognosis in a trial-based cohort of stage II and III CC patients treated with 5-fluorouracil (5-FU)/leucovorin or FOLFIRI.
Tissue specimens of 1254 patients were tested for 10 different loci and were classified as MSI-high (MSI-H) when three or more loci were unstable and MSS otherwise. Study end points were overall survival (OS) and relapse-free survival (RFS).
In stage II, RFS and OS were better for patients with MSI-H than with MSS CC [hazard ratio (HR) 0.26, 95% CI 0.10-0.65, P = 0.004 and 0.16, 95% CI 0.04-0.64, P = 0.01). In stage III, RFS was slightly better for patients with MSI-H CC (HR 0.67, 95% CI 0.46-0.99, P = 0.04), but the difference was not statistically significant for OS (HR 0.70, 95% CI 0.44-1.09, P = 0.11). Outcomes for patients with MSI-H CC were not different between the two treatment arms. RFS was better for patients with MSI-H than with MSS CC in the right and left colon, whereas for OS this was significant only in the right colon. For patients with KRAS- and BRAF-mutated CC, but not for double wild-type patients, RFS and OS were significantly better when the tumors were also MSI-H. An interaction test was statistically significant for KRAS and MSI status (P = 0.005), but not for BRAF status (P = 0.14).
Our results confirm that for patients with stage II CC but less so for those with stage III MSI-H is strongly prognostic for RFS and OS. In the presence of 5-FU treatment, stage II patients with MSI-H tumors maintain their survival advantage in comparison with MSS patients and adding irinotecan has no added benefit. CLINICALTRIALS.GOV IDENTIFIER: NCT00026273.
虽然微卫星不稳定（MSI）的结肠癌（CC）比微卫星稳定（MSS）的 CC 具有更好的预后，但影响因临床病理参数而异。我们研究了 MSI 状态如何影响接受氟尿嘧啶（5-FU）/亚叶酸或 FOLFIRI 治疗的 II 期和 III 期 CC 患者的试验队列中的预后。
对 1254 名患者的组织标本进行了 10 个不同位点的检测，如果有三个或更多位点不稳定，则将其分类为 MSI-高（MSI-H），否则为 MSS。研究终点是总生存（OS）和无复发生存（RFS）。
在 II 期，MSI-H 患者的 RFS 和 OS 均优于 MSS CC 患者[风险比（HR）0.26，95%CI 0.10-0.65，P=0.004 和 0.16，95%CI 0.04-0.64，P=0.01]。在 III 期，MSI-H CC 患者的 RFS 略好（HR 0.67，95%CI 0.46-0.99，P=0.04），但 OS 无统计学差异（HR 0.70，95%CI 0.44-1.09，P=0.11）。MSI-H CC 患者在两种治疗组之间的结局无差异。MSI-H 患者的 RFS 优于 MSS CC 患者的右结肠和左结肠，而 OS 仅在右结肠有显著差异。对于 KRAS 和 BRAF 突变的 CC 患者，但对于双野生型患者，当肿瘤也是 MSI-H 时，RFS 和 OS 明显更好。对于 KRAS 和 MSI 状态的交互测试具有统计学意义（P=0.005），但对于 BRAF 状态则无统计学意义（P=0.14）。
我们的结果证实，对于 II 期 CC 患者，MSI-H 强烈预测 RFS 和 OS，但对于 III 期 CC 患者则不如此。在 5-FU 治疗的情况下，与 MSS 患者相比，MSI-H 肿瘤的 II 期患者保持其生存优势，并且添加伊立替康没有额外获益。CLINICALTRIALS.GOV 标识符：NCT00026273。
