Programa de Pós-Graduação em Medicina: Ciências Gastroenterológicas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Fam Cancer. 2010 Jun;9(2):131-9. doi: 10.1007/s10689-009-9297-x.
Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by germline mutations in one of the mismatch repair (MMR) genes: MLH1, MSH2, MSH6 and PMS2. Clinically, Lynch syndrome is characterized by early onset (45 years) of colorectal cancer (CRC), as well as extra-colonic cancer. Male and female carriers of Lynch syndrome-associated mutations have different lifetime risks for CRC and in women endometrial cancer (EC) may be the most common tumor. Whenever Amsterdam criteria are not fulfilled, the currently recommended laboratory screening strategies involve microsatellite instability testing and immunohistochemistry staining of the tumor for the major MMR proteins. The aim of this study was to estimate the frequency of MMR deficiencies in women diagnosed with EC who are at-risk for Lynch syndrome. Thirty women diagnosed with EC under the age of 50 years and/or women with EC and a first degree relative diagnosed with a Lynch syndrome-associated tumor were included. To assess MMR deficiencies four methods were used: multiplex PCR, Single Strand Conformation Polymorphism, Immunohistochemistry and Methylation Specific-Multiplex Ligation-dependent Probe Amplification. Twelve (40%) patients with EC fulfilling one of the inclusion criteria had results indicative of MMR deficiency. The identification of 5 women with clear evidence of MMR deficiency and absence of either Amsterdam or Bethesda criteria among 10 diagnosed with EC under the age of 50 years reinforces previous suggestions by some authors that these women should be considered at risk and always screened for Lynch syndrome after informed consent.
林奇综合征是一种常染色体显性遗传的癌症易感性综合征，由错配修复（MMR）基因中的种系突变引起：MLH1、MSH2、MSH6 和 PMS2。临床上，林奇综合征的特征是结直肠癌（CRC）的发病年龄较早（45 岁），以及结外癌症。林奇综合征相关突变的男性和女性携带者患 CRC 的终生风险不同，而女性子宫内膜癌（EC）可能是最常见的肿瘤。只要不符合阿姆斯特丹标准，目前推荐的实验室筛查策略包括微卫星不稳定性检测和肿瘤中主要 MMR 蛋白的免疫组织化学染色。本研究旨在估计诊断为 EC 且有林奇综合征风险的女性中 MMR 缺陷的频率。共纳入 30 名年龄在 50 岁以下被诊断为 EC 的女性和/或患有 EC 且一级亲属被诊断为林奇综合征相关肿瘤的女性。为了评估 MMR 缺陷，使用了四种方法：多重 PCR、单链构象多态性、免疫组织化学和甲基化特异性-多重连接依赖性探针扩增。符合纳入标准之一的 12 名（40%）EC 患者存在 MMR 缺陷的结果。在 10 名年龄在 50 岁以下被诊断为 EC 的患者中，有 5 名明确证据表明存在 MMR 缺陷且缺乏阿姆斯特丹或贝塞斯达标准，这进一步证实了一些作者的先前建议，即这些女性应被视为有风险，并在知情同意后始终筛查林奇综合征。
