Früher Verlust der Heterozygotie auf Chromosomenarm 16q in flachen epithelialen Atypien der Brust : Detektion durch Mikrosatellitenanalysen (Beste Forschungsbeiträge: Gynäkopathologie)

With the improvement of breast carcinoma screening, pre-malignant cell lesions such as flat epithelial atypia (FEA) are detected more frequently. Several studies have demonstrated that FEA show features of a ductal neoplasia, but is it really a precursor lesion? We have started a comparative genetic analysis of a panel of nine microsatellite markers on six different chromosomal regions to investigate whether FEAs show the same characteristic genetic alterations as ductal carcinomas in situ (DCISs) and invasive carcinoma of the breast. FEAs, DCISs and invasive carcinomas of the same patients were microdissected using PALM micro laser technology. DNA was isolated using the QIAamp DNA Micro Kit (QIAGEN). We have investigated a set of the polymorphic microsatellite markers D7S522, D8S522, NEFL, D10S541 (PTEN), D13S153 (RB1), D16S400, D16S402, D16S422 and D17S855 (BRCA1) using multiplex PCR for the detection of allelic imbalances. Most of the investigated FEAs showed a lower frequency of loss of heterozygosity than associated DCISs or invasive carcinomas. However, we were able to detect the same alterations in FEAs as in DCISs or invasive carcinomas in a number of cases. Notably, the microsatellite marker on 16q showed more prevalent allelic imbalances in FEAs than the other investigated markers. One of the hallmarks in the pathogenesis of a large subgroup of invasive breast carcinomas is the early loss of chromosome arm 16q. In this study, we were able to detect frequent genetic alterations on chromosome 16q in FEAs, associated DCISs and invasive carcinomas. This suggests that FEA is a precursor lesion in the low-grade pathway.