Microsatellite instability screening in colorectal carcinoma: immunohistochemical analysis of MMR proteins in correlation with clinicopathological features and Ki-67 protein expression

Noha N. Yassen, Dalia M. Abouelfadl, Naglaa F. Abbas, Ahmed S. A. Soliman, Marwa E. Shabana
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Abstract

Abstract Background Defects in mismatch repair (MMR) system or microsatellite instability (MSI) and detected in colorectal carcinoma (CRC), both in sporadic and more frequently in hereditary cases. Immunohistochemistry (IHC) is the most frequent method for MMR protein deficiency screening in CRCs. In this study, we aimed to evaluate immunohistochemical expression of MMR and Ki-67 in colorectal carcinoma with clinicopathological features. Methods In this study, we evaluated the immunohistochemical expression of MMR proteins including MSH6, MSH2, PMS2 and MLH1 in 50 resection materials with colorectal carcinoma. Their expression is correlated with clinicopathological features of patients together, with Ki-67 protein expression in attempt to screen the most significant predictor of microsatellite instability. Results Of the 50 cases of cancer colon, 28% were classified as MSI-H, 20% were MSI-L, and 52% were MSS. The most frequent pattern in MSI-H tumors was concurrent loss of MSH6 and PMS2 proteins. There was a significant correlation between MMR protein expression pattern with tumor size, grade, T-classification and stage (0.015, 0.0515, 0.0162 and 0.0391), respectively. MSI-H tumors were located more frequently in right colon, early TNM stage and poorly differentiated and infrequent distant metastases. There was a significant correlation between Ki-67 high expression and MSI status patterns in their common biological aspects distinct from MSI-negative tumors . Conclusions Mismatch repair defective colorectal carcinoma has characteristics clinicopathological features different from MSS tumors. The role of immunohistochemistry (IHC) for MSI evaluation is the easiest and effective way for evaluation of MMR deficiency in colorectal carcinoma.
结直肠癌微卫星不稳定性筛查:MMR蛋白与临床病理特征和Ki-67蛋白表达的相关免疫组织化学分析
背景错配修复(MMR)系统或微卫星不稳定性(MSI)缺陷在结直肠癌(CRC)中检测到,既见于散发性病例,也见于遗传性病例。免疫组织化学(IHC)是筛查crc中MMR蛋白缺乏最常用的方法。在本研究中,我们旨在评估MMR和Ki-67在具有临床病理特征的结直肠癌中的免疫组织化学表达。方法在本研究中,我们评估了50例结直肠癌切除材料中MMR蛋白MSH6、MSH2、PMS2和MLH1的免疫组织化学表达。它们的表达与患者的临床病理特征相关,Ki-67蛋白表达试图筛选微卫星不稳定性的最重要预测因子。结果50例结肠癌中,MSI-H占28%,MSI-L占20%,MSS占52%。MSI-H肿瘤中最常见的模式是MSH6和PMS2蛋白同时缺失。MMR蛋白表达谱与肿瘤大小、分级、t分型、分期的相关性分别为0.015、0.0515、0.0162、0.0391。MSI-H肿瘤多见于右结肠、TNM早期、低分化和少见的远处转移。Ki-67高表达与MSI状态模式在不同于MSI阴性肿瘤的共同生物学方面存在显著相关性。结论错配修复缺陷型结直肠癌具有不同于MSS肿瘤的临床病理特征。免疫组织化学(IHC)评价MSI是评价结直肠癌MMR缺乏最简单、最有效的方法。
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