Chromosomal Imbalances are Associated with Metastasis-Free Survival in Breast Cancer Patients

Multiple chromosomal imbalances have been identified in breast cancer using comparative genomic hybridization (CGH). Their association with the primary tumors' potential for building distant metastases is unknown. In this study we have investigated 39 invasive breast carcinomas with a mean foll...

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Main Authors: Michaela Aubele, Gert Auer, Herbert Braselmann, Jörg Nährig, Horst Zitzelsberger, Leticia Quintanilla‐Martinez, Jan Smida, Axel Walch, Heinz Höfler, Martin Werner
Format: Article
Language:English
Published: Wiley 2002-01-01
Series:Analytical Cellular Pathology
Online Access:http://dx.doi.org/10.1155/2002/820269
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author Michaela Aubele
Gert Auer
Herbert Braselmann
Jörg Nährig
Horst Zitzelsberger
Leticia Quintanilla‐Martinez
Jan Smida
Axel Walch
Heinz Höfler
Martin Werner
author_facet Michaela Aubele
Gert Auer
Herbert Braselmann
Jörg Nährig
Horst Zitzelsberger
Leticia Quintanilla‐Martinez
Jan Smida
Axel Walch
Heinz Höfler
Martin Werner
author_sort Michaela Aubele
collection DOAJ
description Multiple chromosomal imbalances have been identified in breast cancer using comparative genomic hybridization (CGH). Their association with the primary tumors' potential for building distant metastases is unknown. In this study we have investigated 39 invasive breast carcinomas with a mean follow‐up period of 99 months (max. 193 months) by CGH to determine the prognostic value of chromosomal gains and losses. The mean number of chromosomal imbalances per tumor was 6.5±0.7 (range 2 to 18). The most frequent alterations identified in more than 1/3 of cases were gains on chromosomes 11q13, 12q24, 16, 17, and 20q, and losses on 2q and 13q. A significantly different frequency of chromosomal aberrations (p≤0.05) was found between DNA‐diploid and non‐diploid tumors (gain on chromosome 17). Differences were also noted between tumors progressing to distant metastases within the period of follow‐up and those which do not (gains on 11q13 and 12q24; loss on 12q). Significant univariate correlations (p≤0.05) with the metastasis‐free survival of patients were found for lymph node status, the cytometrical determined DNA ploidy (diploid/non‐diploid) and anisokaryosis, and for DNA gains on 11q13, 12q24, 17, and 18p. An unexpected inverse correlation was found between clinical outcome and gains on 11q13 and 12q24. In multivariate analysis independent prognostic value, in addition to lymph node status, was found for chromosomal gains on 11q13, 12q24, 17 and 18p. Amplification on 20q, which did not correlate with metastasis‐free survival in a univariate analysis, showed weak prognostic significance in combination with the nodal status. The prognostic value of chromosomal alterations – some of them by inverse correlation – suggests an interaction and/or compensation of the involved amplified genes and their effects on the occurrence of distant metastases in breast cancer patients.
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spelling doaj-art-d1082ba0dd994a648424beb4dfb5eaca2025-08-20T03:19:38ZengWileyAnalytical Cellular Pathology0921-89121878-36512002-01-01242-3778710.1155/2002/820269Chromosomal Imbalances are Associated with Metastasis-Free Survival in Breast Cancer PatientsMichaela Aubele0Gert Auer1Herbert Braselmann2Jörg Nährig3Horst Zitzelsberger4Leticia Quintanilla‐Martinez5Jan Smida6Axel Walch7Heinz Höfler8Martin Werner9GSF – Research Center for Environment and Health, Institute of Pathology, D‐85764 Neuherberg, GermanyInstitute of Radiobiology, D‐85764 Neuherberg, GermanyDepartment of Oncology and Pathology, Karolinska Institutet and Hospital, S‐17176 Stockholm, SwedenTechnische Universität, Institute of Pathology, D‐81675 München, GermanyDepartment of Oncology and Pathology, Karolinska Institutet and Hospital, S‐17176 Stockholm, SwedenGSF – Research Center for Environment and Health, Institute of Pathology, D‐85764 Neuherberg, GermanyTechnische Universität, Institute of Pathology, D‐81675 München, GermanyTechnische Universität, Institute of Pathology, D‐81675 München, GermanyGSF – Research Center for Environment and Health, Institute of Pathology, D‐85764 Neuherberg, GermanyTechnische Universität, Institute of Pathology, D‐81675 München, GermanyMultiple chromosomal imbalances have been identified in breast cancer using comparative genomic hybridization (CGH). Their association with the primary tumors' potential for building distant metastases is unknown. In this study we have investigated 39 invasive breast carcinomas with a mean follow‐up period of 99 months (max. 193 months) by CGH to determine the prognostic value of chromosomal gains and losses. The mean number of chromosomal imbalances per tumor was 6.5±0.7 (range 2 to 18). The most frequent alterations identified in more than 1/3 of cases were gains on chromosomes 11q13, 12q24, 16, 17, and 20q, and losses on 2q and 13q. A significantly different frequency of chromosomal aberrations (p≤0.05) was found between DNA‐diploid and non‐diploid tumors (gain on chromosome 17). Differences were also noted between tumors progressing to distant metastases within the period of follow‐up and those which do not (gains on 11q13 and 12q24; loss on 12q). Significant univariate correlations (p≤0.05) with the metastasis‐free survival of patients were found for lymph node status, the cytometrical determined DNA ploidy (diploid/non‐diploid) and anisokaryosis, and for DNA gains on 11q13, 12q24, 17, and 18p. An unexpected inverse correlation was found between clinical outcome and gains on 11q13 and 12q24. In multivariate analysis independent prognostic value, in addition to lymph node status, was found for chromosomal gains on 11q13, 12q24, 17 and 18p. Amplification on 20q, which did not correlate with metastasis‐free survival in a univariate analysis, showed weak prognostic significance in combination with the nodal status. The prognostic value of chromosomal alterations – some of them by inverse correlation – suggests an interaction and/or compensation of the involved amplified genes and their effects on the occurrence of distant metastases in breast cancer patients.http://dx.doi.org/10.1155/2002/820269
spellingShingle Michaela Aubele
Gert Auer
Herbert Braselmann
Jörg Nährig
Horst Zitzelsberger
Leticia Quintanilla‐Martinez
Jan Smida
Axel Walch
Heinz Höfler
Martin Werner
Chromosomal Imbalances are Associated with Metastasis-Free Survival in Breast Cancer Patients
Analytical Cellular Pathology
title Chromosomal Imbalances are Associated with Metastasis-Free Survival in Breast Cancer Patients
title_full Chromosomal Imbalances are Associated with Metastasis-Free Survival in Breast Cancer Patients
title_fullStr Chromosomal Imbalances are Associated with Metastasis-Free Survival in Breast Cancer Patients
title_full_unstemmed Chromosomal Imbalances are Associated with Metastasis-Free Survival in Breast Cancer Patients
title_short Chromosomal Imbalances are Associated with Metastasis-Free Survival in Breast Cancer Patients
title_sort chromosomal imbalances are associated with metastasis free survival in breast cancer patients
url http://dx.doi.org/10.1155/2002/820269
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