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Breast Cancer Research
Published in: Breast Cancer Research 5/2008

Open Access 01-10-2008 | Research article

Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9

Authors: Dengfeng Cao, Kornelia Polyak, Marc K Halushka, Hind Nassar, Nina Kouprina, Christine Iacobuzio-Donahue, Xinyan Wu, Saraswati Sukumar, Jessica Hicks, Angelo De Marzo, Pedram Argani

Published in: Breast Cancer Research | Issue 5/2008

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Abstract

Introduction

Although lobular carcinoma in situ (LCIS) has traditionally been viewed as a marker of breast cancer risk, recent clinical, pathological and genetic analyses have supported the concept that LCIS is a low risk, direct precursor of invasive lobular carcinoma. Global gene expression profiling of LCIS has not been performed.

Methods

We analysed the comprehensive gene expression profile of a unique case of mass-forming LCIS using serial analysis of gene expression (SAGE). This SAGE library is publicly available online. By comparing the gene expression profile of LCIS to that of benign breast epithelium and stroma, we identified several genes up and down regulated in LCIS. Differential expression of selected genes not previously studied in LCIS was validated at the protein level by immunohistochemistry and at the RNA level by quantitative reverse transcriptase PCR (RT-PCR).

Results

We identified down regulation of claudin 4 and overexpression of matrix metalloproteinase 9 in LCIS relative to normal breast epithelium and stroma. We validated these findings by immunohistochemistry in a separate series of 11 and 19 LCIS cases, respectively. Overexpression of matrix metalloproteinase 9 was further confirmed by quantitative RT-PCR analysis of the index case.

Conclusions

We have created the first global gene expression profile of LCIS, and demonstrated down regulation of cell junction proteins (an expected result) and overexpression of matrix metalloproteinase 9 (an unexpected result). Additional analysis of this data made available as an online resource should facilitate further molecular characterisation of LCIS.
Appendix
Available only for authorised users
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Metadata
Title
Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9
Authors
Dengfeng Cao
Kornelia Polyak
Marc K Halushka
Hind Nassar
Nina Kouprina
Christine Iacobuzio-Donahue
Xinyan Wu
Saraswati Sukumar
Jessica Hicks
Angelo De Marzo
Pedram Argani
Publication date
01-10-2008
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2008
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2189

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