[Early loss of heterozygosity on chromosome arm 16q in flat epithelial atypia of the breast. Detection by microsatellite analyses].
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.
Schmidt
H
H
Gerhard Domagk Institut für Pathologie, Molekulare Pathologie, Universitätsklinikum Münster, Domagkstrasse 17, 48149 Münster. schmidha@uni-muenster.de
Dahrenmöller
C
C
Agelepoulos
K
K
Hungermann
D
D
Böcker
W
W
D022981:Allelic Imbalance; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002114:Calcinosis / Q000235:genetics / Q000473:pathology; D044584:Carcinoma, Ductal / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D018895:Microsatellite Repeats; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D011379:Prognosis