Laser microdissection and microsatellite analyses of breast cancer reveal a high degree of tumor heterogeneity

Carcinomas with productive fibrosis are the most common forms of breast can cer. Analysis of tumor-specific genomic alterations can be compromised by t he presence of normal cells, demanding microdissection of small tumor areas to detect loss of heterozygosity (LOH) and microsatellite instability (MSI ). The aim of this study was to evaluate the importance of precise laser mi crodissection for microsatellite analyses and investigation of tumor hetero geneity in breast cancer. 39 primary breast tumor samples were analyzed for MSI and LOH by PCR followed by polyacrylamide gel electrophoresis and silv er staining using 15 microsatellite markers. Different tumor areas were pro cessed separately in 30 patients. Both intraductal and invasive breast canc er regions were investigated in 11 patients. The following results were obt ained: (1) accurate microdissection revealed MSI in 3 or more of the invest igated markers (greater than or equal to 20%) in 33% of the patients, a hig her frequency than reported previously; (2) laser microdissection was 43% m ore sensitive in detection of LOH compared to manual microdissection due to a reduction of contamination by normal cells, and (3) 29 of 30 investigate d tumors showed heterogeneity of genetic alterations in different tumor reg ions. Laser-based microdissection is a valuable tool in genetic analysis of desmoplastic tumors and allows an accurate determination of genetic altera tions in histologically different tumor regions. Copyright (C) 2001 S. Karg er AG, Basel.