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Amplification of Growth Regulatory Genes in Intraductal Breast Cancer Is Associated with Higher Nuclear Grade but Not with the Progression to Invasiveness
- Source :
- Laboratory Investigation. 81:565-571
- Publication Year :
- 2001
- Publisher :
- Elsevier BV, 2001.
-
Abstract
- Ductal carcinoma in situ (DCIS), as an identifiable progenitor lesion of invasive breast cancer, represents a morphologically, biologically, and prognostically heterogeneous disease. It is not clear which molecular mechanisms are involved in progression to infiltrative growth. In this study, 83 DCIS classified according to the Van Nuys grading scheme were examined for amplification of growth regulatory genes that have been found to be amplified in invasive breast cancer (c-erbB2, topoisomerase IIalpha, c-myc, and cyclinD1 genes). Exact quantification of gene amplification was enabled by a combination of laser microdissection of paraffin-embedded tissue with real-time PCR. In DCIS, gene amplifications of all tested genes were found. The most frequently amplified gene was c-erbB2 found in 21 of 83 (25%) cases. Amplification of the other genes under investigation was observed in 4% to 6% of cases, high-grade DCIS being predominantly affected. High-grade DCIS differed significantly from low- and intermediate-grade DCIS in frequency and level of c-erbB2 amplification. In addition, high-grade DCIS revealed an accumulation of genetic aberrations. Amplification status in pure in situ lesions did not differ from intraductal carcinoma with an infiltrative component, indicating that although associated with a higher nuclear grade gene amplification might not represent an independent prognostic marker of disease progression.
- Subjects :
- Pathology
medicine.medical_specialty
Mammary gland
Breast Neoplasms
Biology
Pathology and Forensic Medicine
Breast cancer
Gene duplication
medicine
Carcinoma
Humans
Neoplasm Invasiveness
Growth Substances
skin and connective tissue diseases
neoplasms
Molecular Biology
Grading (tumors)
Laser capture microdissection
Cell Nucleus
Carcinoma, Ductal, Breast
Gene Amplification
Cell Biology
Genes, erbB-2
Ductal carcinoma
medicine.disease
Gene Expression Regulation, Neoplastic
Carcinoma, Intraductal, Noninfiltrating
medicine.anatomical_structure
Tumor progression
Disease Progression
Cancer research
Female
Subjects
Details
- ISSN :
- 00236837
- Volume :
- 81
- Database :
- OpenAIRE
- Journal :
- Laboratory Investigation
- Accession number :
- edsair.doi.dedup.....23f65fd9eef88833757bd2caf4af6300