Cytogenetic alterations and cytokeratin expression patterns in breast cancer

Integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis

Eberhard Korsching, Jens Packeisen, Konstantin Agelopoulos, Martin Eisenacher, Reinhard Voss, Jorma Isola, Paul J. Van Diest, Burkhard Brandt, Werner Boecker, Horst Buerger

Research output: Contribution to journalArticle

Abstract

The introduction of a concept proposing multiple cellular subgroups in the normal female breast, including cytokeratin 5/6 (Ck 5/6)-positive progenitor cells, offers a new explanation for the existence of highly aggressive breast cancers with and without Ck 5/6 expression. Using the tissue microarray technique, 166 breast cancer cases, all characterized by comparative genomic hybridization, were evaluated by immunohistochemistry, using 15 different antibodies (estrogen receptor, progesterone receptor, p53, Ki-67, c-erbB2, epidermal growth factor receptor, cyclins A, D1, and E, bcl-2, p21, p27, Ck 5/6, Ck 8/18, and smooth muscle actin) and chromogenic in situ hybridization for c-erbB2. Biomathematical cluster analysis was applied to confirm the conventional interpretation of the results by an independent approach. Ck 5/6-positive breast carcinomas were in general negative for estrogen receptor and progesterone receptor, were highly proliferating (as reflected by Ki67 and cyclin A), and were associated with specific protein expression patterns, such as expression of p53 and epithelial growth factor receptor (all related to more aggressive tumor behavior), which could further be demonstrated by biomathematical cluster analysis. In contrast Ck 5/6-negative breast carcinomas revealed a lower tumor proliferation rate, an increased expression of p21, p27, c-erbB2, and bcl-2, and a significantly lower number of genetic alterations, with losses of chromosomal material of 16q as the most common genetic alteration. Our data give the first hints to the hypothesis that different cellular subgroups in the female breast give rise to subgroups of breast carcinomas with differing protein expression and cytogenetic alteration patterns that may be related to clinical behavior.

Original languageEnglish (US)
Pages (from-to)1525-1533
Number of pages9
JournalLaboratory Investigation
Volume82
Issue number11
StatePublished - Nov 1 2002
Externally publishedYes

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Keratin-6
Keratin-5
Keratins
Cytogenetics
Carcinogenesis
Breast
Breast Neoplasms
Cyclin A
Progesterone Receptors
Estrogen Receptors
Cluster Analysis
Cyclin E
Comparative Genomic Hybridization
Growth Factor Receptors
Cyclin D1
Epidermal Growth Factor Receptor
In Situ Hybridization
Smooth Muscle
Actins
Neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Cytogenetic alterations and cytokeratin expression patterns in breast cancer : Integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis. / Korsching, Eberhard; Packeisen, Jens; Agelopoulos, Konstantin; Eisenacher, Martin; Voss, Reinhard; Isola, Jorma; Van Diest, Paul J.; Brandt, Burkhard; Boecker, Werner; Buerger, Horst.

In: Laboratory Investigation, Vol. 82, No. 11, 01.11.2002, p. 1525-1533.

Research output: Contribution to journalArticle

Korsching, E, Packeisen, J, Agelopoulos, K, Eisenacher, M, Voss, R, Isola, J, Van Diest, PJ, Brandt, B, Boecker, W & Buerger, H 2002, 'Cytogenetic alterations and cytokeratin expression patterns in breast cancer: Integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis', Laboratory Investigation, vol. 82, no. 11, pp. 1525-1533.
Korsching, Eberhard ; Packeisen, Jens ; Agelopoulos, Konstantin ; Eisenacher, Martin ; Voss, Reinhard ; Isola, Jorma ; Van Diest, Paul J. ; Brandt, Burkhard ; Boecker, Werner ; Buerger, Horst. / Cytogenetic alterations and cytokeratin expression patterns in breast cancer : Integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis. In: Laboratory Investigation. 2002 ; Vol. 82, No. 11. pp. 1525-1533.
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abstract = "The introduction of a concept proposing multiple cellular subgroups in the normal female breast, including cytokeratin 5/6 (Ck 5/6)-positive progenitor cells, offers a new explanation for the existence of highly aggressive breast cancers with and without Ck 5/6 expression. Using the tissue microarray technique, 166 breast cancer cases, all characterized by comparative genomic hybridization, were evaluated by immunohistochemistry, using 15 different antibodies (estrogen receptor, progesterone receptor, p53, Ki-67, c-erbB2, epidermal growth factor receptor, cyclins A, D1, and E, bcl-2, p21, p27, Ck 5/6, Ck 8/18, and smooth muscle actin) and chromogenic in situ hybridization for c-erbB2. Biomathematical cluster analysis was applied to confirm the conventional interpretation of the results by an independent approach. Ck 5/6-positive breast carcinomas were in general negative for estrogen receptor and progesterone receptor, were highly proliferating (as reflected by Ki67 and cyclin A), and were associated with specific protein expression patterns, such as expression of p53 and epithelial growth factor receptor (all related to more aggressive tumor behavior), which could further be demonstrated by biomathematical cluster analysis. In contrast Ck 5/6-negative breast carcinomas revealed a lower tumor proliferation rate, an increased expression of p21, p27, c-erbB2, and bcl-2, and a significantly lower number of genetic alterations, with losses of chromosomal material of 16q as the most common genetic alteration. Our data give the first hints to the hypothesis that different cellular subgroups in the female breast give rise to subgroups of breast carcinomas with differing protein expression and cytogenetic alteration patterns that may be related to clinical behavior.",
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AU - Voss, Reinhard

AU - Isola, Jorma

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AU - Buerger, Horst

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