Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal cancer syndrome
Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal cancer syndrome
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DOI：
10.1007/s10549-009-0449-3
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发表时间：
2010-04-01
影响因子：
3.8
通讯作者：
Nilbert, Mef
中科院分区：
文献类型：
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作者：
Jensen, Uffe Birk;Sunde, Lone;Nilbert, Mef
乳腺癌是否可以是遗传性非息肉病性结直肠癌（HNPCC）综合征的一个特征一直存在争议。为了阐明错配修复缺陷（MMR）是否确实在乳腺癌中发挥作用，我们使用丹麦HNPCC登记来确定所有发生在MMR基因突变携带者中的乳腺癌。总共有20名女性突变携带者在平均50岁时被诊断为乳腺癌。这些肿瘤主要是导管癌，在8/14例评价的肿瘤中有广泛的淋巴细胞反应。MMR蛋白免疫染色显示MLH 1、MSH 2或MSH 6表达缺失，对应于在所研究的16例病例中的7例中鉴定的突变，并且这些肿瘤在平均50（33-66）岁时被诊断。在所研究的相当大比例的乳腺癌中，MMR缺陷的证明将另一种肿瘤类型与HNPCC联系起来。虽然低的数字不激励监测，我们的观察支持缺陷MMR在乳腺癌进展中的作用HNPCC，大概是通过加速积累的突变乳腺癌相关基因。
Whether or not breast cancer can be a feature of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome has been debated. In order to clarify if defective mismatch repair (MMR) may indeed play a role in breast cancer, we used the Danish HNPCC register to identify all breast cancers that occurred in MMR gene mutation carriers. In total, 20 female mutation carriers were diagnosed with breast cancer at mean 50 years of age. These tumors were predominantly ductal carcinomas with extensive lymphocytic reactions in 8/14 evaluated tumors. MMR protein immunostaining showed loss of expression of MLH1, MSH2 or MSH6 corresponding to the mutations identified in 7 of the 16 cases investigated, and these tumors were diagnosed at mean 50 (33-66) years of age. The demonstration of defective MMR in a substantial proportion of the breast cancers studied links yet another tumor type to HNPCC. Though the low number do not motivate surveillance, our observation supports a role for defective MMR in breast cancer progression in HNPCC, presumably through accelerated accumulation of mutations in breast cancer-associated genes.