首页 > 期刊杂志 > 正文

Lynch Syndrome Screening in the Gynecologic Tract: Current State of the Art.

妇科肿瘤的Lynch综合征筛选现状

Abstract

Lynch syndrome underlies approximately 5% of endometrial cancers and ∼1% of ovarian cancers. Gynecologic malignancies are often the presenting cancer in these patients. Therefore, there is considerable benefit to identifying these patients and enrolling them and affected family members in surveillance programs for secondary malignancies. The molecular basis for Lynch syndrome is a defect in the DNA mismatch repair (MMR) system. Tumors can be screened for these defects using immunohistochemistry to identify loss of MMR proteins or by enlisting polymerase chain reaction to identify the microsatellite instability that attends dysfunctional MMR. However, diagnostic confirmation of Lynch syndrome requires germline mutational testing. The algorithm for screening endometrial carcinomas for Lynch syndrome remains a subject of debate, with some studies supporting universal screening and others proposing a hybrid approach informed by clinicopathologic features. This review discusses the rationales and relative merits of current Lynch syndrome-screening approaches for endometrial and ovarian cancers and provides pathologists with an informed approach to Lynch syndrome testing in gynecologic cancers. It also addresses the clinical difficulties presented by cases with discordant screening and germline results (Lynch-like cancers) and emphasizes the critical role of strong communication with clinician and genetic counseling colleagues to ensure that the significance of a positive screening test is appropriately conveyed to patients. Finally, it discusses the need for more nuanced cost-effective analyses and the potential role for next-generation sequencing panels in future screening efforts.

摘要

Lynch综合征约占子宫内膜癌的5%和卵巢癌的1%左右。妇科恶性肿瘤常为Lynch综合征的首发表现。因此,监测这类患者以及受累家属有利于防治原发和继发的肿瘤。Lynch综合征的分子基础是DNA错配修复(MMR)系统的缺陷,筛选方法包括用免疫组织化学来识别MMR蛋白的丢失以及用PCR以确定微卫星不稳定性。Lynch综合征的确诊需要生殖突变检测。子宫内膜癌患者的Lynch综合征筛选仍然有争议,有研究支持普遍筛查而其他人则提出结合临床病理的综合筛选方法。本文回顾了当前子宫内膜癌和卵巢癌的Lynch综合征筛查方法的优缺点,为病理学家提供了妇科癌症患者筛选Lynch综合征的方法,另外讨论了一般筛查和生殖突变检测结果不一致(Lynch样癌)的临床困境,并强调临床医生和遗传咨询人员的有效沟通,以确保患者理解阳性筛查结果的的意义。最后,本文讨论了详尽进行成本效益分析的必要性和二代测序(NGS)在今后筛查工作中的潜在作用。


full text

我要评论

0条评论