Association Between Microsatellite Instability (MSI) based on MLH1 and PMS2 Marker with Clinicopathological Features of Colorectal Cancer Patients

Rizka Vidya, Lestari, R. V. Lestari, Neni Arshita, Dewi Kartikawati Paramita, Susana H. Hutajulu
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Abstract

Background: Microsatellite instability (MSI) is one of the important pathways involved in development of colorectal cancer (CRC). MSI occurs due to mutations or hypermethylation of negative MMR proteins MLH1 and PMS2. The accumulation of mutations at microsatellite locus accelerated the development of CRC. Characteristics of CRC patients with MSI are not sensitive to 5FU chemotherapy and have a good clinical outcomes that can be used as a prognostic factor and a predictor of therapy. Therefore MSI detection is needed. Method: A retrospective cross-sectional study of 80 CRC slides obtained from DR. Sardjito Hospital Yogyakarta and clinical laboratory in 2010-2016. Immunohistochemical staining with anti-MLH1 and anti PMS2 antibodies to see MSI status. Negative MLH1 expression is called MSI MLH1 positive and PMS2 negative expression is called positive MSI PMS2. The association between MSI MLH1 and PMS2 with clinicopathology parameters was analyzed using Chi square. Results: Colorectal cancer patients MSI MLH1 as much as 44 (61.1%), MSI PMS2 as much as 21 (29.2%) and, MSI MLH1 and PMS2 simultaneously as much as 18 (25.0%). MSI MLH1 and PMS2 positive are found in ≥50 years old. The number of male patients is more than women. Most of the patients had a T3-T4 tumor size with advanced stage and well differentiated. MSI MLH1 associated with tumor differentiation (p = 0.011). Conclusion: MSI MLH1 is associated with tumor differentiation (p = 0.011), but, no association with the other clinicopathology parameters. MSI PMS2 is not associated to the overall clinicopathology parameters. MSI MLH1 and PMS2 are not simultaneously associated with all clinicopathology parameters (p> 0.05)
基于MLH1和PMS2标记的微卫星不稳定性(MSI)与结直肠癌患者临床病理特征的关系
背景:微卫星不稳定性(Microsatellite instability, MSI)是参与结直肠癌(CRC)发生发展的重要途径之一。MSI的发生是由于MMR阴性蛋白MLH1和PMS2的突变或超甲基化。微卫星位点突变的积累加速了结直肠癌的发展。结直肠癌合并MSI患者的特点对5FU化疗不敏感,临床预后良好,可作为预后因素和治疗预测因素。因此需要MSI检测。方法:对2010-2016年DR. Sardjito医院和临床实验室获得的80张结直肠癌切片进行回顾性横断面研究。用抗mlh1和抗PMS2抗体免疫组化染色观察MSI状态。MLH1阴性表达称为MSI MLH1阳性,PMS2阴性表达称为MSI PMS2阳性。采用卡方分析MSI MLH1和PMS2与临床病理参数的关系。结果:结直肠癌患者MSI MLH1最多44例(61.1%),MSI PMS2最多21例(29.2%),同时MSI MLH1和PMS2最多18例(25.0%)。MSI、MLH1和PMS2阳性见于≥50岁。男性患者的数量多于女性。多数患者肿瘤大小为T3-T4,肿瘤分期晚期,分化良好。MSI MLH1与肿瘤分化相关(p = 0.011)。结论:MSI MLH1与肿瘤分化相关(p = 0.011),但与其他临床病理参数无关。MSI PMS2与总体临床病理参数无关。MSI MLH1和PMS2与所有临床病理参数不同时相关(p < 0.05)。
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