Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an EPCAM-MSH2 fusion.
Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an EPCAM-MSH2 fusion.
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具有 EPCAM-MSH2 融合的 Lynch 综合征患者的细胞质 MSH2 免疫反应性。
DOI：
10.1111/his.13104
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发表时间：
2017
期刊：
影响因子：
6.4
通讯作者：
Sugano K.
中科院分区：
文献类型：
--
作者：
Sekine S;Ogawa R;Saito S;Ushiama M;Shida D;Nakajima T;Taniguchi H;Hiraoka N;Yoshida T;Sugano K.
目的 错配修复 (MMR) 蛋白的免疫组织化学越来越多地用于检查肿瘤中的 MMR 状态。本文的目的是报告一例林奇综合征结肠癌患者的病例，该患者表现出异常的细胞质错配修复蛋白定位。方法和结果组织学上，结肠癌被诊断为髓样癌，伴有明显的肿瘤浸润淋巴细胞和克罗恩病样反应。免疫组织化学显示 MSH2 在非肿瘤细胞中的细胞质和核中表达，而在肿瘤细胞中仅在细胞质中表达。 MSH6 在非肿瘤细胞中表达于细胞核，但在肿瘤细胞中缺失。 MLH1 和 PMS2 的核表达在非肿瘤细胞和肿瘤细胞中均保留。肿瘤的微卫星不稳定性很高，这表明 MMR 功能有缺陷。随后的种系突变分析发现跨越 EPCAM 3' 区域和 MSH2 5' 区域的基因组缺失，导致 EPCAM 和 MSH2 的框内融合。结论 MSH2 异常的细胞质免疫反应性被认为是由于非功能性 EPCAM-MSH2 融合产物所致。本病例说明，MMR 蛋白不仅表达缺失，而且定位异常，都表明 MMR 系统有缺陷。
AimsImmunohistochemistry for mismatch repair (MMR) proteins is being increasingly used to examine MMR status in tumours. The aim of the present article was to report the case of a colon cancer patient with Lynch syndrome who showed unusual cytoplasmic MMR protein localization.Methods and resultsHistologically, the colon cancer was diagnosed as medullary carcinoma associated with prominent tumour‐infiltrating lymphocytes and a Crohn's‐like reaction. Immunohistochemistry revealed cytoplasmic and nuclear expression of MSH2 in non‐neoplastic cells, and exclusively cytoplasmic expression in tumour cells. MSH6 expression was nuclear in non‐neoplastic cells, but was lost in tumour cells. Nuclear expression of MLH1 and PMS2 was retained in both non‐neoplastic and tumour cells. The tumour was microsatellite instability‐high, which is indicative of defective MMR function. A subsequent germline mutation analysis identified a genomic deletion spanning the 3′ region ofEPCAMand the 5′ region ofMSH2, resulting in an in‐frame fusion ofEPCAMandMSH2.ConclusionsThe unusual cytoplasmic immunoreactivity of MSH2 was considered to be attributable to the non‐functional EPCAM–MSH2 fusion product. The present case illustrates that not only loss of expression, but also abnormal localization, of MMR proteins is indicative of a defective MMR system.