Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysisReportar como inadecuado

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BMC Cancer

, 7:55

First Online: 27 March 2007Received: 27 November 2006Accepted: 27 March 2007DOI: 10.1186-1471-2407-7-55

Cite this article as: Turashvili, G., Bouchal, J., Baumforth, K. et al. BMC Cancer 2007 7: 55. doi:10.1186-1471-2407-7-55


BackgroundInvasive 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.

MethodsWe 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.

ResultsUsing 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.

ConclusionIDC 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.

AbbreviationsADAM12ADAM metallopeptidase domain 12



CTHRC1Collagen triple helix repeat containing 1

DAVIDDatabase for Annotation, Visualization and Integrated Discovery

DDR1Discoidin domain receptor 1

DVL1Human homolog of the Drosophila dishevelled gene

ECMExtracellular matrix

EMP1Epithelial membrane antigen 1

EMTEpithelial-mesenchymal transition

EREstrogen receptor

GCOSGeneChip Operating Software

IDCInvasive ductal carcinoma

ILCInvasive lobular carcinoma

ISHIn situ hybridization

IVTIn vitro transcription

PCRPolymerase chain reaction

PgRProgesterone receptor

RMARobust multiarray analysis

RNARibonucleic acid

RPRank products analysis

SFRP1Secreted frizzled-related protein 1

TDLUTerminal duct lobular unit

TGFβTransforming growth factor β

TMATissue microarray

WISP1WNT1 inducible signaling pathway protein 1.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-7-55 contains supplementary material, which is available to authorized users.

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Autor: Gulisa Turashvili - Jan Bouchal - Karl Baumforth - Wenbin Wei - Marta Dziechciarkova - Jiri Ehrmann - Jiri Klein - Eduard 


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