Caldés T, Perez-Segura P, Tosar A, de La Hoya M, Diaz-Rubio E
Laboratory of Molecular Oncology, San Carlos University Hospital, Madrid, Spain.
Teratog Carcinog Mutagen. 2000;20(5):283-91.
In some tumors, defects in mismatch repair enzymes lead to errors in the replication of simple nucleotide repeat segments RER+ tumors. This condition is commonly known as microsatellite instability (MSI) because of the frequent mutations of microsatellite sequences. Although the MSI phenotype is well recognized in some colon, gastric, pancreatic, and endometrial cancers, reports of MSI in breast cancer are inconsistent. The purpose of this study was to determine the presence of MSI in breast cancer and to correlate its occurrence with clinicopathological parameters, including expression of estrogen and progesterone receptors. We analyzed the status of 10 different microsatellite loci (mono- and dinucleotide repeats). In this study, microsatellite size patterns were compared in 88 paired breast-cancer/peripheral-blood DNA samples. Fluorescent polymerase chain reaction (PCR) for typing microsatellites coupled with DNA fragment analysis in an automated DNA sequencer was applied. MSI in at least two microsatellite markers was observed in 6 out of 88 (7%) of the cases, all belonging to Stage II or III. These MSI data were analyzed using a range of clinicopathological parameters; no correlation between MSI and histopathological characteristics were found. A significant correlation was observed between MSI and negative expression of both estrogen and progesterone receptors (P<0.02), indicating a possible relationship between specific genetic changes at these microsatellite regions and hormonal deregulation in the progression of breast cancer.
在一些肿瘤中，错配修复酶的缺陷会导致简单核苷酸重复序列复制错误（RER+肿瘤）。由于微卫星序列频繁突变，这种情况通常被称为微卫星不稳定性（MSI）。尽管MSI表型在某些结肠癌、胃癌、胰腺癌和子宫内膜癌中已得到充分认识，但关于乳腺癌中MSI的报道并不一致。本研究的目的是确定乳腺癌中MSI的存在情况，并将其发生与临床病理参数相关联，包括雌激素和孕激素受体的表达。我们分析了10个不同微卫星位点（单核苷酸和二核苷酸重复）的状态。在本研究中，对88对乳腺癌/外周血DNA样本的微卫星大小模式进行了比较。应用荧光聚合酶链反应（PCR）对微卫星进行分型，并结合自动DNA测序仪进行DNA片段分析。在88例病例中有6例（7%）观察到至少两个微卫星标记存在MSI，所有这些病例均属于II期或III期。使用一系列临床病理参数对这些MSI数据进行了分析；未发现MSI与组织病理学特征之间存在相关性。观察到MSI与雌激素和孕激素受体的阴性表达之间存在显著相关性（P<0.02），表明这些微卫星区域的特定基因变化与乳腺癌进展中的激素失调之间可能存在关联。
