Cytogenetic and fluorescence in situ hybridization analysis of breast fibroadenomas

doi:10.1016/0165-4608(92)90060-L

Cancer Genetics and Cytogenetics

Volume 63, Issue 1, 1 October 1992, Pages 32-36

https://doi.org/10.1016/0165-4608(92)90060-L Get rights and content

Abstract

We report cytogenetic and fluorescence in situ hybridization (FISH) analysis findings in 7 patients with breast fibroadenomas (FA). Three patients were cytogenetically abnormal. One patient had a translocation t(3;5)(p22;q13), the second had trisomy 8, and the third had two clones, 47,XX,+11 and 47,XX,+10.

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We applied a comparative genomic hybridization (CGH) technique to paraffin-embedded tissue samples taken from fibroadenomas, benign breast tumors, to detect possible numerical and unbalanced genetic changes. We compared the results to those from previous cytogenetic studies of fibroadenomas. In concurrence with previous cytogenetic studies of fibroadenomas, we detected genetic aberrations in chromosomes 4–6, 8–13, 16, 18, 19, 20, and 22. In addition, with the CGH technique we were able to find two new aberrations, 15q+ and 16p−. Because these aberrations have also been reported to be present in breast cancer, the importance of this finding is yet to be determined.
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Transformation of cells in culture is a model system for carcinogenesis, and two major theories (i.e., mutagenesis and aneuploidy) have emerged from in vitro and in vivo studies. A third view is presented here on the initial steps in the change of primary cells to extended life cells, and their change to immortalized cells. Both changes involve identical, microscopically visible cell abnormalities hitherto dismissed as cell degenerative characteristics. The major cell changes (i.e., giant cells, nuclear fragmentation to form multinucleated cells [MNC]) translated into genetic terms begin with the creation of polyploidy by DNA endoreduplication, followed by amitotic division of these giant cells to produce MNC. Individual nuclei, surrounded by a cell membrane, bud from the surface of the MNC, and represent the origin of the transformed cells. Induced budding by a protease treatment of MNC suggests that the extracellular matrix is an inhibitor of the budding process from human MNC. The production of the MNC is a genetic process determined by two abnormal events (i.e., overproduction of DNA and amitotic chromosomal segregation) during which there are possibilities for different genetic mechanisms to produce inherited variability within and between MNC. These concepts are discussed in regard to carcinogenesis, and by extension its possible prevention by use of the special cytopathic cell changes in carcinogen testing and in clinical screening programs.
Clonal chromosomal alterations in fibroadenomas of the breast
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A cytogenetic study on short-term cell cultures from 10 fibroadenomas of the breast is reported. Clonal chromosomal alterations were observed in all cases analyzed, involving preferentially chromosomes X, 12, 14, 20, and 22. Normal karyotypes were found in 34.9% of the cells. The present findings are discussed together with the reports on fibroadenomas and other benign lesions of the breast described in the literature. Although no specific chromosome abnormality to date can be attributed to a particular type of benign breast pathology, some recurrent alterations are starting to emerge and may characterize these benign breast lesions, differentiating them from their malignant counterparts.
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Gynecomastia is a benign condition that frequently occurs in the male breast gland; however, the cytogenetic data on this entity are very limited. To our knowledge, three cases have been reported in the literature, and the only one with an abnormal karyotype had a concomitant breast carcinoma. In this study we report clonal chromosomal alterations in a gynecomastia sample without any signs of adjacent malignant tissue. The nonrandom abnormalities observed were a deletion of 12p, monosomies of chromosomes 9, 17, 19, and 20, and the presence of a marker chromosome. Most of these alterations have been previously described in the literature in other breast lesions, including benign and malignant (male and female) tumors, indicating their recurrence and nonrandomness in abnormal processes of the mammary gland.
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Cytogenetic and fluorescence in situ hybridization analysis of breast fibroadenomas

Abstract

Cancer Genet Cytogenet

Anal Biochem

Breast Disorders

Fibro-adenoma of the breast

Br J Surg

Benign Disorders and Diseases of the Breast: Concepts and Clinical Management

Combined immuno-histochemical/cytogenetic (IH/C) approach reveals lineage specificity of chromosome aberrations: Application to solid tumors (abstract)

Am J Hum Genet

Carcinoma arising within fibroadenomas of the breast: A clinicopathologic study of 105 patients

Am J Clin Pathol

Chromosome abnormalities in breast fibroadenomas

Genes Chromosomes Cancer