Ribic Christine M, Sargent Daniel J, Moore Malcolm J, Thibodeau Stephen N, French Amy J, Goldberg Richard M, Hamilton Stanley R, Laurent-Puig Pierre, Gryfe Robert, Shepherd Lois E, Tu Dongsheng, Redston Mark, Gallinger Steven
Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto.
N Engl J Med. 2003 Jul 17;349(3):247-57. doi: 10.1056/NEJMoa022289.
Colon cancers with high-frequency microsatellite instability have clinical and pathological features that distinguish them from microsatellite-stable tumors. We investigated the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II and stage III colon cancer.
Tumor specimens were collected from patients with colon cancer who were enrolled in randomized trials of fluorouracil-based adjuvant chemotherapy. Microsatellite instability was assessed with the use of mononucleotide and dinucleotide markers.
Of 570 tissue specimens, 95 (16.7 percent) exhibited high-frequency microsatellite instability. Among 287 patients who did not receive adjuvant therapy, those with tumors displaying high-frequency microsatellite instability had a better five-year rate of overall survival than patients with tumors exhibiting microsatellite stability or low-frequency instability (hazard ratio for death, 0.31 [95 percent confidence interval, 0.14 to 0.72]; P=0.004). Among patients who received adjuvant chemotherapy, high-frequency microsatellite instability was not correlated with increased overall survival (hazard ratio for death, 1.07 [95 percent confidence interval, 0.62 to 1.86]; P=0.80). The benefit of treatment differed significantly according to the microsatellite-instability status (P=0.01). Adjuvant chemotherapy improved overall survival among patients with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability, according to a multivariate analysis adjusted for stage and grade (hazard ratio for death, 0.72 [95 percent confidence interval, 0.53 to 0.99]; P=0.04). By contrast, there was no benefit of adjuvant chemotherapy in the group with high-frequency microsatellite instability.
Fluorouracil-based adjuvant chemotherapy benefited patients with stage II or stage III colon cancer with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability but not those with tumors exhibiting high-frequency microsatellite instability.
高频微卫星不稳定的结肠癌具有一些临床和病理特征，使其有别于微卫星稳定的肿瘤。我们研究了微卫星不稳定状态作为II期和III期结肠癌氟尿嘧啶辅助化疗获益预测指标的有效性。
从参加基于氟尿嘧啶的辅助化疗随机试验的结肠癌患者中收集肿瘤标本。使用单核苷酸和二核苷酸标记评估微卫星不稳定情况。
在570份组织标本中，95份（16.7%）表现出高频微卫星不稳定。在287例未接受辅助治疗的患者中，肿瘤显示高频微卫星不稳定的患者的五年总生存率高于微卫星稳定或低频不稳定肿瘤的患者（死亡风险比，0.31[95%置信区间，0.14至0.72]；P = 0.004）。在接受辅助化疗的患者中，高频微卫星不稳定与总生存率增加无关（死亡风险比，1.07[95%置信区间，0.62至1.86]；P = 0.80）。治疗获益根据微卫星不稳定状态有显著差异（P = 0.01）。根据对分期和分级进行调整的多因素分析，辅助化疗改善了微卫星稳定肿瘤或低频微卫星不稳定肿瘤患者的总生存率（死亡风险比，0.72[95%置信区间，0.53至0.99]；P = 0.04）。相比之下，辅助化疗对高频微卫星不稳定组没有益处。
基于氟尿嘧啶的辅助化疗使微卫星稳定肿瘤或低频微卫星不稳定的II期或III期结肠癌患者获益，但对高频微卫星不稳定肿瘤的患者没有益处。
