高频微卫星不稳定作为预后因素的IV期结直肠癌转移模式
Metastatic Pattern of Stage IV Colorectal Cancer with High-Frequency Microsatellite Instability as a Prognostic Factor.
作者信息
Fujiyoshi Kenji, Yamamoto Gou, Takenoya Takashi, Takahashi Akemi, Arai Yoshiko, Yamada Mina, Kakuta Miho, Yamaguchi Kensei, Akagi Yoshito, Nishimura Yoji, Sakamoto Hirohiko, Akagi Kiwamu
机构信息
Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
Department of Surgery, Kurume University, Fukuoka, Japan.
出版信息
Anticancer Res. 2017 Jan;37(1):239-247. doi: 10.21873/anticanres.11313.
BACKGROUND
A recent clinical trial on the immune check-point inhibitor pembrolizumab demonstrated that microsatellite instability (MSI) is a good biomarker for response to this inhibitor. However, clinicopathological features of advanced colorectal cancer (CRC) with high-frequency MSI (MSI-H) are unclear.
PATIENTS AND METHODS
A total of 2,439 surgically resected CRC tissues were analyzed for MSI status, and mutational status of V-Ki-Ras2 Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF). Stage IV cases were selected, and clinical and molecular features were evaluated.
RESULTS
There was no significant survival difference observed between MSI-H CRC and microsatellite-stable (MSS) CRC in patients with stage IV disease (3.92 vs. 2.50 years; p=0.766). However, hematogenous and lymphogenous metastasis-dominant CRC with MSI-H demonstrated poor prognosis, whereas peritoneal metastasis-dominant CRC with MSI-H demonstrated good prognosis, (1.33 vs. 5.2 years; p=0.006).
CONCLUSION
Prognosis of stage IV CRC with MSI-H depended on the metastatic pattern. These findings provide useful information for the adaptation of CRC immunotherapy.
背景
最近一项关于免疫检查点抑制剂帕博利珠单抗的临床试验表明，微卫星不稳定性（MSI）是对该抑制剂反应的良好生物标志物。然而，高频微卫星不稳定（MSI-H）的晚期结直肠癌（CRC）的临床病理特征尚不清楚。
患者与方法
对总共2439例手术切除的CRC组织进行MSI状态分析，以及V-Ki-Ras2 Kirsten大鼠肉瘤2病毒癌基因同源物（KRAS）、神经母细胞瘤RAS病毒癌基因同源物（NRAS）和v-Raf鼠肉瘤病毒癌基因同源物B（BRAF）的突变状态分析。选择IV期病例，并评估其临床和分子特征。
结果
IV期疾病患者中，MSI-H CRC和微卫星稳定（MSS）CRC之间未观察到显著的生存差异（3.92年对2.50年；p = 0.766）。然而，MSI-H的以血行和淋巴转移为主的CRC预后较差，而MSI-H的以腹膜转移为主的CRC预后良好（1.33年对5.2年；p = 0.006）。
结论
MSI-H的IV期CRC的预后取决于转移模式。这些发现为CRC免疫治疗的应用提供了有用信息。
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