TY - JOUR
T1 - Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9
AU - Cao, Dengfeng
AU - Polyak, Kornelia
AU - Halushka, Marc K.
AU - Nassar, Hind
AU - Kouprina, Nina
AU - Iacobuzio-Donahue, Christine
AU - Wu, Xinyan
AU - Sukumar, Saraswati
AU - Hicks, Jessica
AU - De Marzo, Angelo
AU - Argani, Pedram
N1 - Funding Information:
We thank Jie Lu for performing the MMP-2 and MMP-9 immunohistochemistry. We thank Ralph H. Hruban for critically reviewing this manuscript. We acknowledge the support of the NIH SPORE P50 CA88843 and DOD COE W81XWH-04-1-0595.
PY - 2008/10/27
Y1 - 2008/10/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=59449099748&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59449099748&partnerID=8YFLogxK
U2 - 10.1186/bcr2189
DO - 10.1186/bcr2189
M3 - Article
C2 - 18954444
AN - SCOPUS:59449099748
SN - 1465-5411
VL - 10
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 5
M1 - R91
ER -