微卫星状态与术后大肠癌患者的临床及病理特征相关性研究

  目的  分析微卫星状态与术后大肠癌患者的临床及病理特征的相关性。  方法  选取南京大学医学院附属鼓楼医院2014年6月至2017年6月病理诊断确诊的572例大肠癌患者的临床及病理资料，并对其手术切除标本进行微卫星状态与KRAS、NRAS突变状态的检测，同时采用免疫组织化学法检测组织中Ki-67、EGFR、MGMT及Lgr5的表达情况。按照微卫星不稳定性（microsatellite instability，MSI）状态，分为高度微卫星不稳定（high-frequency MSI，MSI-H）大肠癌组与微卫星稳定状态（microsatellite stability，MSS）和低度微卫星不稳定（low-frequency MSI，MSI-L）大肠癌组，比较组间的临床、病理等资料的差异。  结果  572例大肠癌患者中40例（7.0%）为MSI-H，532例（93.0%）为MSS/MSI-L。与MSS/MSI-L组大肠癌病例相比MSI-H组具有以下特征:1）病灶常位于右半结肠；2）不同年龄段的发病比例相当；3）肿瘤分期较早，即Ⅰ/Ⅱ期分期比例较大（P=0.003）；4）淋巴结转移比例较低（P= 0.023）；5）形成癌结节比例较低（P=0.005）；6）KRAS第2外显子突变率较低（P=0.004），NRAS未突变。两组在MGMT、EGFR、Lgr5、Ki-67免疫组织化学阳性率检测未见显著性差异。  结论  微卫星状态与大肠癌患者的年龄相关，与MSS/MSI-L的大肠癌患者相比，MSI-H的患者具有其特殊的临床病理特征，且NRAS及KRAS第2外显子的突变率低，MGMT甲基化率高，可为大肠癌的个体化诊断和治疗提供依据。 

Study on the relationship between microsatellite status and clinicopathological characteristics of colorectal cancer patients after surgery

  Objective  To evaluate the association of microsatellite status with clinicopathological features of colorectal cancer patients after surgery.  Methods  In total, 572 colorectal cancer cases with clear pathological diagnosis and clinicopathological features from the Department of Pathology, Nanjing Drum Tower Hospital from June 2014 to June 2017 were included in the study. Microsatellite status and RAS mutations were detected by polymerase chain reaction. Ki67, EGFR, MGMT, and Lgr5 were detected by immunohistochemistry. Clinicopathological features were analyzed based on the microsatellite states.  Results  In this study, we found MSI-H in 7.0% of all patients, whereas 93.0% cases showed MSS/MSI-L. Compared with MSS and MSI-L colorectal cancer cases, MSI-H colorectal cancer cases showed the following characteristics: 1) more likely located in the right colon, 2) comparable incidences at different ages, 3) early cancer stage (Ⅰ/Ⅱ)(P=0.003), 4) a lower proportion of lymph node metastasis (P=0.023), 5) a lower proportion of cancerous nodules (P=0.005), 6) a lower mutation rate of KRAS (P=0.004), and no mutation of NRAS. There was no significant difference in the positive rates of MGMT, EGFR, Lgr5, and Ki67 between the two groups.  Conclusions  Compared with MSS/MSI-L patients, MSI-H patients have specific clinicopathological features. A lower mutation rate of KRAS/NRAS and higher methylation rate of MGMT were also found in MSI-H patients. Our results provide a basis for individual diagnosis and treatment in colorectal cancer.