Walsh Michael D, Cummings Margaret C, Buchanan Daniel D, Dambacher Wendy M, Arnold Sven, McKeone Diane, Byrnes Rebecca, Barker Melissa A, Leggett Barbara A, Gattas Michael, Jass Jeremy R, Spurdle Amanda B, Young Joanne, Obermair Andreas
Familial Cancer Laboratory and Molecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research, Herston, Australia.
Clin Cancer Res. 2008 Mar 15;14(6):1692-700. doi: 10.1158/1078-0432.CCR-07-1849. Epub 2008 Feb 29.
A woman with early-onset endometrial cancer (EC) may represent the "sentinel" cancer event in a Lynch syndrome kindred. The aim of this study was to determine the incidence of Lynch syndrome in a series of young-onset EC, and to identify molecular, clinical, and pathologic features that may alert clinicians to the presence of this disorder.
Patients with EC, ages < or =50 years, were identified from the Queensland Centre for Gynaecological Cancer. Tumor sections underwent histopathology review and were immunostained for mismatch repair proteins. Tumor DNA was tested for microsatellite instability and methylation of MLH1. Patients were conservatively classified as presumptive Lynch syndrome if their tumors showed loss of at least one mismatch repair protein and were negative for methylation of MLH1. Personal and family history of cancer was reviewed where available.
Presumptive Lynch syndrome was seen in 26 of 146 (18%) tumors. These tumors were more likely to be poorly differentiated, International Federation of Gynecology and Obstetrics stage II and above, have tumor-infiltrating lymphocytes, have higher mitotic rate, and have deeper myometrial invasion (P < 0.05). Lynch syndrome cases were more likely to be associated with a positive family history when analyzed for Amsterdam criteria II, diagnosis of a Lynch syndrome spectrum cancer in at least one first-degree relative, and family history of any cancer (P < 0.05).
Presumptive Lynch syndrome was identified in 18% of early-onset EC. A risk of this magnitude would argue for routine immunohistochemical testing of tumors in patients diagnosed with EC at or before the age of 50 years.
患有早发性子宫内膜癌（EC）的女性可能代表林奇综合征家族中的“哨兵”癌症事件。本研究的目的是确定一系列年轻发病的EC中林奇综合征的发病率，并识别可能提醒临床医生注意这种疾病存在的分子、临床和病理特征。
从昆士兰妇科癌症中心识别出年龄≤50岁的EC患者。肿瘤切片进行组织病理学检查，并对错配修复蛋白进行免疫染色。检测肿瘤DNA的微卫星不稳定性和MLH1的甲基化。如果患者的肿瘤显示至少一种错配修复蛋白缺失且MLH1甲基化呈阴性，则将其保守分类为疑似林奇综合征。如有可能，会回顾患者个人和家族的癌症病史。
146例肿瘤中有26例（18%）被诊断为疑似林奇综合征。这些肿瘤更可能分化差、国际妇产科联盟分期为II期及以上、有肿瘤浸润淋巴细胞、有较高的有丝分裂率以及有更深的肌层浸润（P<0.05）。根据阿姆斯特丹标准II、至少一名一级亲属诊断为林奇综合征谱系癌症以及任何癌症的家族史进行分析时，林奇综合征病例更可能与阳性家族史相关（P<0.05）。
在18%的早发性EC中发现了疑似林奇综合征。如此高的风险表明应对50岁及以下被诊断为EC的患者的肿瘤进行常规免疫组化检测。
