Type

Journal Article

Authors

William M Gallagher
Michael J Duffy
Finian Martin
Goran Landberg
Karin Jirstrom
Jean McBryan
Robert C Millikan
Shauna Hegarty
Donal J Brennan
Eadaoin McKiernan
and 1 others

Subjects

Microbiology

Topics
carcinoma ductal breast drug therapy claudin 4 female genetics pathology metabolism tissue array analysis carcinoma lobular adenocarcinoma mucinous aged immunoenzyme techniques middle aged gene expression regulation neoplastic membrane proteins tumor markers biological neoplasm recurrence local survival rate oligonucleotide array sequence analysis blotting western cldn4 protein human prognosis aged 80 and over tumor cells cultured neoplasm staging secondary neoplasm invasiveness therapeutic use carcinoma medullary adult humans tamoxifen cohort studies breast neoplasms receptor erbb 2

Increased claudin-4 expression is associated with poor prognosis and high tumour grade in breast cancer. (2009)

Abstract The role of intercellular tight junctions in breast epithelial cells is traditionally thought to be in maintaining polarity and barrier function. However, claudin-4, a tight junction protein, is overexpressed in breast tumour cells compared to normal epithelial cells, which generally corresponds to a loss in polarity. The aim of this study was to investigate the distribution and potential clinical value of claudin-4 in breast cancer, and to evaluate its usefulness as a prognostic and predictive biomarker. Expression of claudin-4 was initially examined by Western blot analysis in a cohort of 88 breast tumours, and was found to correlate positively with tumour grade and negatively with ER. Claudin-4 expression was then evaluated by immunohistochemistry in a larger cohort of 299 tumours represented on a tissue microarray. Claudin-4 expression correlated positively with tumour grade and Her2, and negatively with ER. High claudin-4 expression was also associated with worse breast cancer-specific survival (p = 0.003), recurrence-free survival (p = 0.025) and overall survival (p = 0.034). Multivariate analysis revealed that claudin-4 independently predicted survival in the entire cohort (HR 1.95; 95%CI 1.01-3.79; p = 0.047) and in the ER positive subgroup treated with adjuvant tamoxifen (HR 4.34; 95%CI 1.14-16.53; p = 0.032). This relationship between increased claudin-4 expression and adverse outcome was validated at the mRNA level in a DNA microarray dataset of 295 breast tumours. We conclude that high levels of claudin-4 protein are associated with adverse outcome in breast cancer patients, including the subgroup of patients treated with adjuvant tamoxifen.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

William M Gallagher, Michael J Duffy, Finian Martin, Goran Landberg, Karin Jirstrom, Jean McBryan, Robert C Millikan, Shauna Hegarty, Donal J Brennan, Eadaoin McKiernan and 1 others

Experts in our system

1
William M Gallagher
University College Dublin
Total Publications: 148
 
2
Michael J Duffy
University College Dublin
 
3
Finian Martin
University College Dublin
Total Publications: 81
 
4
Karin Jirstrom
University College Dublin
 
5
Donal J Brennan
University College Dublin