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Published in: BMC Cancer 1/2007

Open Access 01-12-2007 | Research article

Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis

Authors: Gulisa Turashvili, Jan Bouchal, Karl Baumforth, Wenbin Wei, Marta Dziechciarkova, Jiri Ehrmann, Jiri Klein, Eduard Fridman, Jozef Skarda, Josef Srovnal, Marian Hajduch, Paul Murray, Zdenek Kolar

Published in: BMC Cancer | Issue 1/2007

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Abstract

Background

Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells.

Methods

We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR.

Results

Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC.

Conclusion

IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel immunohistochemical markers helpful in distinguishing between IDC and ILC. Further studies with larger sets of patients are needed to verify the gene expression profiles of various histological types of breast cancer in order to determine molecular subclassifications, prognosis and the optimum treatment strategies.
Appendix
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Metadata
Title
Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis
Authors
Gulisa Turashvili
Jan Bouchal
Karl Baumforth
Wenbin Wei
Marta Dziechciarkova
Jiri Ehrmann
Jiri Klein
Eduard Fridman
Jozef Skarda
Josef Srovnal
Marian Hajduch
Paul Murray
Zdenek Kolar
Publication date
01-12-2007
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2007
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-7-55

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