Genetic alterations in presumptive precursor lesions of breast carcinomas

Article type: Research Article

Authors: Aubele, Michaela^; | Werner, Martin | Höfler, Heinz^;

Affiliations: GSF‐National Research Center for Environment and Health, Institute of Pathology Neuherberg, Germany | Technische Universität München, Institute of Pathology, Munich, Germany

Note: [] Corresponding author: Dr. M. Aubele, GSF‐Forschungszentrum für Umwelt und Gesundheit, Institut für Pathologie, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany. Fax: +49 89 3187 3360; E‐mail: [email protected].

Abstract: The hypothetical multistep model of breast carcinogenesis suggests a transition from normal epithelium to invasive carcinoma via intraductal hyperplasia (without and with atypia) and in situ carcinoma. These presumptive precursor lesions are currently defined by their histological features, and their prognosis is imprecisely estimated from indirect epidemiological evidence. Cytogenetic and molecular‐genetic analysis of these lesions give evidence for an accumulation of various genetic alterations during breast tumorigenesis. Using immuno‐histochemistry overexpression of the c‐erbB‐2 oncogene was found in ductal carcinoma in situ (DCIS), but not in atypical intraductal hyperplasia (AIDH) and intraductal hyperplasia (IDH). An expression of mutant p53 tumor suppressor gene as well as expression of cyclin D1 was identified in DCIS. In IDH lesions loss of heterozygosity (LOH) at various loci could be identified, and comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies delivered evidence for DNA amplification on chromosomal region 20q13 in the early stage of IDH. However, little is currently known about genetic alterations in those premalignant lesions, and the chronology of genetic alterations and histopathological changes during carcinogenesis is mainly undiscovered. Figure 1 can be viewed in colour on http://www.esacp.org/acp/2002/24‐23/aubele.htm

Journal: Analytical Cellular Pathology, vol. 24, no. 2-3, pp. 69-76, 2002