Matthews Kellie S, Estes Jacob M, Conner Michael G, Manne Upender, Whitworth Jenny M, Huh Warner K, Alvarez Ronald D, Straughn J Michael, Barnes Mack N, Rocconi Rodney P
Division of Gynecologic Oncology and the Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA.
Obstet Gynecol. 2008 May;111(5):1161-6. doi: 10.1097/AOG.0b013e31817051d9.
To estimate the frequency of mismatch repair deficiencies associated with hereditary nonpolyposis colorectal cancer, or Lynch syndrome, in women less than age 50 with endometrial cancer.
Consecutive patients less than age 50 diagnosed with endometrial adenocarcinoma were identified. Available pathologic specimens were freshly sliced, and protein expression for MLH1, MSH2, MSH6, and PMS2 was evaluated by immunohistochemistry. Slides were scored on a semiquantitative method with complete absence of any of the four proteins suggesting a deficiency. All results were confirmed by microsatellite instability testing.
Sixty-one pathology specimens were analyzed. Twenty-one (34%) of the tumors had absence of staining of at least one of the four mismatch repair proteins determined by immunohistochemistry and confirmed by microsatellite instability testing. Obese patients were less likely than nonobese patients to have a mismatch repair deficiency (21% versus 59%, respectively). Non-obese patients had a relative risk for a mismatch repair deficiency of 5.5 (95% confidence interval 1.6-19.1; P=.01).
Many women diagnosed with endometrial cancer before age 50 will have a mismatch repair deficiency discovered by immunohistochemistry and microsatellite instability testing. A number of young women diagnosed with endometrial cancer will require further genetic testing for mismatch repair mutations.
III.
评估50岁以下子宫内膜癌女性中与遗传性非息肉病性结直肠癌（Lynch综合征）相关的错配修复缺陷的发生率。
确定连续的年龄小于50岁且诊断为子宫内膜腺癌的患者。将可用的病理标本新鲜切片，通过免疫组织化学评估MLH1、MSH2、MSH6和PMS2的蛋白表达。玻片采用半定量方法评分，四种蛋白中任何一种完全缺失提示存在缺陷。所有结果均通过微卫星不稳定性检测进行确认。
分析了61份病理标本。通过免疫组织化学确定并经微卫星不稳定性检测确认，21例（34%）肿瘤存在至少一种错配修复蛋白染色缺失。肥胖患者出现错配修复缺陷的可能性低于非肥胖患者（分别为21%和59%）。非肥胖患者错配修复缺陷的相对风险为5.5（95%置信区间1.6 - 19.1；P = 0.01）。
许多50岁前被诊断为子宫内膜癌的女性将通过免疫组织化学和微卫星不稳定性检测发现错配修复缺陷。一些被诊断为子宫内膜癌的年轻女性需要进一步进行错配修复突变的基因检测。
III级。
