Genetic Instability Promotes the Acquisition of Chromosomal Imbalances in T1b and T1c Breast Adenocarcinomas
In order to evaluate biological and genetic properties of early breast carcinomas we analyzed microdissected tissue from 33 primary breast carcinomas stage T1b and T1c with respect to the nuclear DNA content, the expression pattern of Ki‐67, cyclin A, p27KIP1, p53 and p21WAF1, and chromosomal gains...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2001-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2001/126030 |
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| author | Harald Blegen B. Michael Ghadimi Annukka Jauho Anders Zetterberg Elina Eriksson Gert Auer Thomas Ried |
| author_facet | Harald Blegen B. Michael Ghadimi Annukka Jauho Anders Zetterberg Elina Eriksson Gert Auer Thomas Ried |
| author_sort | Harald Blegen |
| collection | DOAJ |
| description | In order to evaluate biological and genetic properties of early breast carcinomas we analyzed microdissected tissue from 33 primary breast carcinomas stage T1b and T1c with respect to the nuclear DNA content, the expression pattern of Ki‐67, cyclin A, p27KIP1, p53 and p21WAF1, and chromosomal gains and losses. The results show that T1b carcinomas (6–10 mm, n=17) were frequently near‐diploid (53%) with low proliferative activity and staining patterns of p53 and p21WAF1 that suggest the presence of wild type protein. The majority (12/16) of the T1c tumors (11–20 mm), however, was aneuploid, and proliferative activity and p53 expression were increased. Larger tumor size correlated with an increasing number of chromosomal copy number changes and in particular with regional amplifications. High level copy number increases (amplifications), however, were found exclusively in the aneuploid tumors. Amplification events correlated with elevated cyclin A and reduced p27 expression, respectively. Our results suggest that the sequential acquisition of genomic imbalances during tumor progression is accelerated in aneuploid tumors, and may contribute to the increased malignancy potential. |
| format | Article |
| id | doaj-art-d570d9257bee4a73908a0d322db916d1 |
| institution | Kabale University |
| issn | 0921-8912 1878-3651 |
| language | English |
| publishDate | 2001-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-d570d9257bee4a73908a0d322db916d12025-02-03T01:28:37ZengWileyAnalytical Cellular Pathology0921-89121878-36512001-01-0122312313110.1155/2001/126030Genetic Instability Promotes the Acquisition of Chromosomal Imbalances in T1b and T1c Breast AdenocarcinomasHarald Blegen0B. Michael Ghadimi1Annukka Jauho2Anders Zetterberg3Elina Eriksson4Gert Auer5Thomas Ried6Division of Cellular and Molecular Analysis, Department of Oncology–Pathology, Karolinska Institute, Cancer Center Karolinska, R8:04, SE‐171 76, Stockholm, SwedenGenetics Department, Division of Clinical Sciences, National Cancer Institute, NIH, Building 9, Room 1N105, 9 Memorial Drive, Bethesda, MD 20892, USAGenetics Department, Division of Clinical Sciences, National Cancer Institute, NIH, Building 9, Room 1N105, 9 Memorial Drive, Bethesda, MD 20892, USADivision of Cellular and Molecular Analysis, Department of Oncology–Pathology, Karolinska Institute, Cancer Center Karolinska, R8:04, SE‐171 76, Stockholm, SwedenDivision of Cellular and Molecular Analysis, Department of Oncology–Pathology, Karolinska Institute, Cancer Center Karolinska, R8:04, SE‐171 76, Stockholm, SwedenDivision of Cellular and Molecular Analysis, Department of Oncology–Pathology, Karolinska Institute, Cancer Center Karolinska, R8:04, SE‐171 76, Stockholm, SwedenGenetics Department, Division of Clinical Sciences, National Cancer Institute, NIH, Building 9, Room 1N105, 9 Memorial Drive, Bethesda, MD 20892, USAIn order to evaluate biological and genetic properties of early breast carcinomas we analyzed microdissected tissue from 33 primary breast carcinomas stage T1b and T1c with respect to the nuclear DNA content, the expression pattern of Ki‐67, cyclin A, p27KIP1, p53 and p21WAF1, and chromosomal gains and losses. The results show that T1b carcinomas (6–10 mm, n=17) were frequently near‐diploid (53%) with low proliferative activity and staining patterns of p53 and p21WAF1 that suggest the presence of wild type protein. The majority (12/16) of the T1c tumors (11–20 mm), however, was aneuploid, and proliferative activity and p53 expression were increased. Larger tumor size correlated with an increasing number of chromosomal copy number changes and in particular with regional amplifications. High level copy number increases (amplifications), however, were found exclusively in the aneuploid tumors. Amplification events correlated with elevated cyclin A and reduced p27 expression, respectively. Our results suggest that the sequential acquisition of genomic imbalances during tumor progression is accelerated in aneuploid tumors, and may contribute to the increased malignancy potential.http://dx.doi.org/10.1155/2001/126030 |
| spellingShingle | Harald Blegen B. Michael Ghadimi Annukka Jauho Anders Zetterberg Elina Eriksson Gert Auer Thomas Ried Genetic Instability Promotes the Acquisition of Chromosomal Imbalances in T1b and T1c Breast Adenocarcinomas Analytical Cellular Pathology |
| title | Genetic Instability Promotes the Acquisition of Chromosomal Imbalances in T1b and T1c Breast Adenocarcinomas |
| title_full | Genetic Instability Promotes the Acquisition of Chromosomal Imbalances in T1b and T1c Breast Adenocarcinomas |
| title_fullStr | Genetic Instability Promotes the Acquisition of Chromosomal Imbalances in T1b and T1c Breast Adenocarcinomas |
| title_full_unstemmed | Genetic Instability Promotes the Acquisition of Chromosomal Imbalances in T1b and T1c Breast Adenocarcinomas |
| title_short | Genetic Instability Promotes the Acquisition of Chromosomal Imbalances in T1b and T1c Breast Adenocarcinomas |
| title_sort | genetic instability promotes the acquisition of chromosomal imbalances in t1b and t1c breast adenocarcinomas |
| url | http://dx.doi.org/10.1155/2001/126030 |
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