TY - JOUR
T1 - Cytogenetic alterations and cytokeratin expression patterns in breast cancer
T2 - Integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis
AU - Korsching, Eberhard
AU - Packeisen, Jens
AU - Agelopoulos, Konstantin
AU - Eisenacher, Martin
AU - Voss, Reinhard
AU - Isola, Jorma
AU - Van Diest, Paul J.
AU - Brandt, Burkhard
AU - Boecker, Werner
AU - Buerger, Horst
N1 - Funding Information:
This work was supported by grants from Deutsche Krebshilfe (10-1681-Bü-I) and Innovative Medizinische Forschung (Bü220018). Address reprint requests to: Dr. H. Bürger, Institute of Pathology, University of Münster, Domagkstr. 17, 48149 Münster, Germany. E-mail: burgerh@uni-muenster.de
PY - 2002/11
Y1 - 2002/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036849017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036849017&partnerID=8YFLogxK
U2 - 10.1097/01.LAB.0000038508.86221.B3
DO - 10.1097/01.LAB.0000038508.86221.B3
M3 - Article
C2 - 12429812
AN - SCOPUS:0036849017
SN - 0023-6837
VL - 82
SP - 1525
EP - 1533
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 11
ER -