title: Invasive tubular carcinoma of the breast frequently is clonally related to flat epithelial atypia and low-grade ductal carcinoma in situ.
abstract: 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.
authors.affiliation: Institute of Pathology, Heidelberg University, Heidelberg, Germany. sebastian.aulmann@med.uni-heidelberg.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Aulmann
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Elsawaf
authors.forename: Roland
authors.initials: R
authors.lastname: Penzel
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Sinn
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D002999:Clone Cells; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000032:analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary
chemical_list: D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm