Kim Jeong Eun, Hong Yong Sang, Kim Hwa Jung, Kim Kyu-Pyo, Kim Sun Young, Lim Seok-Byung, Park In Ja, Kim Chan Wook, Yoon Yong Sik, Yu Chang Sik, Kim Jin Cheon, Kim Ji Hun, Kim Tae Won
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Preventive Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Ann Surg Oncol. 2017 May;24(5):1289-1294. doi: 10.1245/s10434-016-5682-5. Epub 2016 Nov 16.
The impact of microsatellite instability (MSI) on survival in stage III colon cancer treated with adjuvant 5-fluorouracil-oxaliplatin combination (FOLFOX) chemotherapy is not clear. We evaluated the association between MSI and survival in this population.
We analyzed 598 patients with curatively resected stage III colon cancer treated with adjuvant FOLFOX chemotherapy. We determined MSI status using polymerase chain reaction amplification; tumors were classified as high MSI (MSI-H, ≥2 unstable markers), low MSI (MSI-L, 1 unstable marker), or microsatellite stable (MSS, no unstable marker).
Of 598 patients, 8.4% showed MSI-H. Tumors classified as MSI-H were more commonly located in the ascending colon (54.0 vs. 27.7%, p < 0.0001) and had poorly differentiated features (32.0 vs. 8.0%, p < 0.0001). After the median follow-up of 52.8 months, 5-year disease-free (DFS) and overall survival (OS) rates were 77.0 and 85.9%, respectively. In univariate analysis, pathologic T4 (pT4) and pathologic N2 (pN2) was associated with reduced DFS (p < 0.0001 and p < 0.0001, respectively) and OS (p = 0.002 and p = 0.001, respectively), whereas MSI status did not affect either DFS (p = 0.114) or OS (p = 0.525). In patients with pN2 tumors; however, MSI-H was associated with better survival compared with MSS/MSI-L; DFS and OS in patients with MSI-H/pN2 were comparable to those in patients with pN1 tumors.
In patients with stage III colon cancer treated with adjuvant FOLFOX, pT4 and pN2 was associated with reduced survival, but MSI status alone did not affect survival.
微卫星不稳定性（MSI）对接受辅助性5-氟尿嘧啶-奥沙利铂联合（FOLFOX）化疗的III期结肠癌患者生存的影响尚不清楚。我们评估了该人群中MSI与生存之间的关联。
我们分析了598例接受辅助性FOLFOX化疗且已行根治性切除的III期结肠癌患者。我们使用聚合酶链反应扩增来确定MSI状态；肿瘤被分类为高度微卫星不稳定（MSI-H，≥2个不稳定标志物）、低度微卫星不稳定（MSI-L，1个不稳定标志物）或微卫星稳定（MSS，无不稳定标志物）。
在598例患者中，8.4%表现为MSI-H。分类为MSI-H的肿瘤更常见于升结肠（54.0%对27.7%，p<0.0001），且具有低分化特征（32.0%对8.0%，p<0.0001）。在中位随访52.8个月后，5年无病生存率（DFS）和总生存率（OS）分别为77.0%和85.9%。在单因素分析中，病理T4（pT4）和病理N2（pN2）与DFS降低相关（分别为p<0.0001和p<0.0001）以及OS降低相关（分别为p=0.002和p=0.001），而MSI状态对DFS（p=0.114）或OS（p=0.525）均无影响。然而，在pN2肿瘤患者中，与MSS/MSI-L相比，MSI-H与更好的生存相关；MSI-H/pN2患者的DFS和OS与pN1肿瘤患者相当。
在接受辅助性FOLFOX治疗的III期结肠癌患者中，pT4和pN2与生存率降低相关，但单独的MSI状态不影响生存。
