Toward new strategies to select young endometrial cancer patients for mismatch repair gene mutation analysis
Toward new strategies to select young endometrial cancer patients for mismatch repair gene mutation analysis
复制标题
DOI：
10.1200/jco.2003.04.094
复制
发表时间：
2003-12-01
影响因子：
45.3
通讯作者：
van der Zee, AGJ
中科院分区：
文献类型：
--
作者：
Berends, MJW;Wu, Y;van der Zee, AGJ
目的：确定50岁以下诊断的子宫内膜癌患者中错配修复（MMR）基因生殖系突变的频率;将突变的存在与家族史、组织病理学数据、肿瘤微卫星不稳定性（MSI）的存在和免疫染色相关联;并制定这些患者的基因检测标准。子宫内膜癌患者（N = 58），诊断年龄小于50岁，被纳入并询问他们的家族史。对MLH 1、MSH 2和MSH 6基因进行突变分析（变性梯度凝胶电泳和序列分析以检测小突变，多重连接依赖性探针扩增以检测大缺失或重复）。对于MSI分析，五个共识标记，和免疫染色的三个MMR蛋白performed.Results：在22例患者中有5个一级家族史的遗传性非息肉病性结直肠癌（HNPCC）相关的癌症，致病性种系突变被发现（MLH 1，3 MSH 2，和MSH 6）。四个突变携带者属于符合修订后的阿姆斯特丹标准的家庭。在35例无家族史的患者中未发现突变（P = 0.006）。57例肿瘤中20例检测到MSI，其中4例为突变携带者。在23的51个癌症，一个或多个MMR蛋白是不存在的，在所有5个突变携带者，免疫染色表明参与MMR gene.Conclusion：在23%的年轻子宫内膜癌患者至少有一个一级亲属与HNPC相关的癌症，MMR基因突变检测。因此，一级亲属中存在HNPC相关癌症似乎是突变分析的重要选择标准。MMR蛋白的后续免疫染色将指向应该分析的基因。(C)2003年，美国临床肿瘤学会。
Purpose: To determine the frequency of mismatch repair (MMR) gene germline mutations in endometrial cancer patients who were diagnosed at less than 50 years of age; to relate the presence of mutations to family history, histopathologic data, presence of tumor microsatellite instability (MSI), and immunostaining; and to formulate criteria for genetic testing in these patients.Patients and Methods: Endometrial cancer patients (N = 58), who were diagnosed at less than 50 years of age, were included and questioned about their family history. Mutation analysis of the MLH1, MSH2, and MSH6 genes was performed (denaturing gradient gel electrophoresis and sequence analysis to detect small mutations and multiplex ligation-dependent probe amplification to detect large deletions or duplications). For MSI analysis, five consensus markers were used, and immunostaining of the three MMR proteins was performed.Results: In five of 22 patients with a positive first-degree family history for hereditary nonpolyposis colorectal cancer (HNPCC)-related cancers, pathogenic germline mutations were found (one MLH1, three MSH2, and one MSH6). Four mutation carriers belonged to families fulfilling the revised Amsterdam criteria. No mutations were found in the 35 patients without such family history (P = .006). MSI was detected in 20 of 57 cancers, among which four were from mutation carriers. In 23 of 51 cancers, one or more MMR protein was absent; in all five mutation carriers, immunostaining indicated the involved MMR gene.Conclusion: In 23% of the young endometrial cancer patients with at least one first-degree relative with an HNPCC-related cancer, an MMR gene mutation was detected. Therefore, presence of an HNPCC-related cancer in a first-degree relative seems to be an important selection criterion for mutation analysis. Subsequent immunostaining of MMR proteins will point to the gene(s) that should be analyzed. (C) 2003 by American Society of Clinical Oncology.