title: Ductal carcinoma in situ of the breast with different histopathological grades and corresponding new breast tumour events: analysis of loss of heterozygosity.
abstract: To compare chromosomal alterations in ductal carcinoma in situ (DCIS) of different histopathological grades and to study aberrations between primary DCIS and corresponding ipsi- or contralateral new in situ or invasive tumours, a study was undertaken of the pattern of loss of heterozygosity (LOH) at chromosomal regions in which LOH has previously been described in invasive breast cancer. LOH was analysed using 19 microsatellite markers located on chromosomes 3p, 6q, 8p, 8q, 9p, 11p, 11q, 16q, 17p, and 17q in 30 women with a primary DCIS. Eleven women with DCIS of grade 1 and 19 with grade 3 according to the EORTC classification system were included. In six patients LOH was also analysed in a subsequent new breast cancer. Fractional allelic loss (FAL, the ratio of chromosomal arms where allelic loss was detected divided by the total number of chromosomal arms with informative markers) was statistically significantly higher in grade 1 DCIS compared with grade 3 (p=0.02) for the 19 loci, indicating that the amount of allelic loss does not correlate with increasing aggressiveness of the studied tumours. Also observed was a complete heterogeneity of LOH in the primary DCIS and their corresponding new events, suggesting that these events probably developed from genetically divergent clones.
authors.affiliation: Department of Oncology-Pathology, Radiumhemmet Cancer Centre Karolinska, Karolinska Institute and Hospital, S-171 76 Stockholm, Sweden. johanna.smeds@cck.ki.se
authors.forename: Johanna
authors.initials: J
authors.lastname: Smeds
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wärnberg
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Norberg
authors.forename: Hans
authors.initials: H
authors.lastname: Nordgren
authors.forename: Lars
authors.initials: L
authors.lastname: Holmberg
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D018895:Microsatellite Repeats; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013548:Sweden
chemical_list: D005819:Genetic Markers