Aulmann Sebastian, Elsawaf Zeinab, Penzel Roland, Schirmacher Peter, Sinn Hans Peter
Institute of Pathology, Heidelberg University, Heidelberg, Germany.
Am J Surg Pathol. 2009 Nov;33(11):1646-53. doi: 10.1097/PAS.0b013e3181adfdcf.
Low-grade precursor lesions, such flat epithelial atypia (FEA), low-grade ductal carcinoma in situ (lg-DCIS), and lobular neoplasia (LN) often coexist with invasive tubular carcinomas (TCs) of the breast. To evaluate a possible clonal relationship, we have examined a series of 27 TC and the surrounding putative precursor lesions using loss of heterozygosity analysis and mitochondrial DNA sequencing. In these lesions (22 FEA, 10 lg-DCIS, 3 LN), loss of heterozygosity was most frequently observed on the long arm of chromosome 16 as well as at chromosome 8p21, 3p14, 1p36 and 11q14 with a high degree of homology of allelic losses between FEA, lg-DCIS and tubular carcinomas. In the adjacent invasive tubular carcinomas, mitochondrial DNA sequencing revealed identical mutation patterns in 50% of the lg-DCIS and in 12 of 21 (57%) informative cases of FEA. No direct association was seen between TC and LN or columnar cell lesions without nuclear atypia. Our data indicate, that in the majority of cases lg-DCIS and FEA are directly related to tubular breast cancer with a possible precursor role.
低级别前驱病变，如扁平上皮异型增生（FEA）、低级别导管原位癌（lg-DCIS）和小叶瘤变（LN），常与乳腺浸润性小管癌（TC）共存。为评估可能的克隆关系，我们使用杂合性缺失分析和线粒体DNA测序，检测了一系列27例TC及其周围假定的前驱病变。在这些病变（22例FEA、10例lg-DCIS、3例LN）中，杂合性缺失最常出现在16号染色体长臂以及8p21、3p14、1p36和11q14染色体上，FEA、lg-DCIS和小管癌之间等位基因缺失具有高度同源性。在相邻的浸润性小管癌中，线粒体DNA测序显示，50%的lg-DCIS以及21例有信息价值的FEA病例中的12例（57%）存在相同的突变模式。未发现TC与LN或无核异型性的柱状细胞病变之间有直接关联。我们的数据表明，在大多数情况下，lg-DCIS和FEA与乳腺小管癌直接相关，可能起前驱作用。
