Trabelsi Mona, Farah Faten, Blel Ahlem, Jaafoura Mohamed Habib, Kharrat Maher, Rammeh Soumaya
Tunis Med. 2017 Dec;95(12):229-236.
The identification essentially of hMSH2 and/or hMLH1 alterations has clinical implications for recognition and prognosis of MSI phenotypes cases. In this study, we tried to identify instability by immunohistochemical expression pattern analysis, compared the results with molecular investigation and shown their usefulness as predictive factors for determination of Microsatellite Instability in patients with colorectal carcinomas in routinely.
Forty seven colorectal cancers and their adjacent colonic mucosa were selected retrospectively for this study. We first studied the potential value of molecular investigation to identify microsatellite instability in which a NCI panel (or Bethesda panel) of five microsatellite was analyzed (Bat-25, Bat-26, D2S123, D5S346 and D17S250). Secondary, we evaluated the immunohistochemical assessment of hMLH1, hMSH2, hMSH6 and PMS2 proteins in tumor and adjacent normal colorectal mucosa tissues.
Fourteen cases were scored as MSI and the remaining MSS. Moreover, we found loss of expression for hMLH1, hMSH2, hMSH6 and PMS2 respectively in 9, 10, 6 and 9 of cases. The MSI patients were less than 45 years old, have right localization and mucinous histological type. We found an association between MSH2, age (P=0.03) and staging (P=0.02). MLH1 is associated only with age (P=0.02) while MSH6 with tumor grade (P=0.01).
We found an association between MSI molecular investigation and MMR immunohistochemical expression which may allow one to specifically identify MSI phenotype of patients with colorectal carcinomas. Furthermore, immunohistochemical analysis of MMR protein can be used in routinely for detection of microsatellite instability without occurs to molecular investigation.
hMSH2和/或hMLH1改变的鉴定对微卫星高度不稳定（MSI）表型病例的识别和预后具有临床意义。在本研究中，我们试图通过免疫组化表达模式分析来鉴定不稳定性，将结果与分子检测进行比较，并展示其作为常规检测结直肠癌患者微卫星不稳定性预测因子的实用性。
本研究回顾性选取了47例结直肠癌及其相邻结肠黏膜。我们首先研究了分子检测在鉴定微卫星不稳定性方面的潜在价值，其中分析了一个由五个微卫星组成的NCI panel（或贝塞斯达panel）（Bat-25、Bat-26、D2S123、D5S346和D17S250）。其次，我们评估了肿瘤和相邻正常结直肠黏膜组织中hMLH1、hMSH2、hMSH6和PMS2蛋白的免疫组化评估。
14例被评为MSI，其余为微卫星稳定（MSS）。此外，我们分别在9例、10例、6例和9例病例中发现了hMLH1、hMSH2、hMSH6和PMS2的表达缺失。MSI患者年龄小于45岁，肿瘤位于右侧，组织学类型为黏液性。我们发现MSH2与年龄（P = 0.03）和分期（P = 0.02）之间存在关联。MLH1仅与年龄相关（P = 0.02），而MSH6与肿瘤分级相关（P = 0.01）。
我们发现MSI分子检测与错配修复（MMR）免疫组化表达之间存在关联，这可能使人们能够特异性地识别结直肠癌患者的MSI表型。此外，MMR蛋白的免疫组化分析可常规用于检测微卫星不稳定性，而无需进行分子检测。
