摘要：Lynch综合征(lynch syndrome, LS)的特征是DNA错配修复(mismatch repair, MMR)基因的胚系突变，受累患者具有患多种癌症的高风险。尽管上尿路的尿路上皮癌(upper tract urothelial carcinoma, UTUC)是LS患者第三常见的恶性肿瘤，但目前仅对结直肠癌和子宫内膜癌推荐应用免疫组织化学(immunohistochemistry, IHC)检测 MMR 蛋白缺失。为了探究在UTUC患者中普遍进行MMR IHC筛查是否适宜，我们以膀胱尿路上皮癌(bladder urothelial cardnoma, BUC)为对比，研究了 MMR在UTUC中的表达和微卫星状态，并对UTUC的临床病理特征进行了评估。我们发现，9%的UTUC显示MMR IHC缺失(8例仅有MSH6缺失；1例为MSH2和MSH6缺失；1例为MLH1和PMS2缺失；n = 117)，而BUC的缺失率仅有1%(仅1例MSH6缺失；n = 160)(p = 0.001)。在这些病例中，分子检测显示，4/10 (40%)的UTUC存在微卫星高度不稳定性(占全部UTUC的3%； 3例仅有MSH6缺失；1例为MLH1和PMS2缺失)，而BUC中无1例检测出微卫星高度不稳定性(P = 0.03)。预测由MMR缺失的唯一临床病理特征是患者既往结直肠癌病史(p=0.0003)。然而，LS患者发生UTUC和结肠癌的发病年龄相似，因此，UTUC可能是某些LS患者的首发肿瘤(前哨事件)。将我们的结果与其他研究结合显示，1% ~ 3%的UTUC病例可能是LS相关癌。2% ~ 6%的结直肠癌和子宫内膜癌病例与LS相关。LS在UTUC中的实际比例可能与之类似，因此我们建议，诊断指南应推荐对所有UTUC进行MMR IHC筛查和微卫星不稳定性检测。

　　关键词：上尿路，尿路上皮，Lynch综合征，错配修复，微卫星不稳定性

（Am J Surg Pathol 2018;42:1549-1555）

美国外科病理学杂志中文版2019年第2期全文No.4

（侯 静/郑林茂  翻译 周 桥 审校）

 

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