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

Fiona Lanigan, Eadaoin McKiernan, Donal J. Brennan, Shauna Hegarty, Robert C. Millikan, Jean McBryan, Karin Jirström, Göran Landberg, Finian Martin, Michael J. Duffy, William M. Gallagher

Research output: Contribution to journalArticlepeer-review

Abstract

The role of intercellular tight junctions in breast epithelia[ cells is traditionaliy 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 Hcr2, and negatively with ER. High claudin-4 expression was also associated with worse breast cancer-specific survival (p = 0.0031), 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 (FIR 4.34; 95%C1 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. (C) 2008 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)2088-2097
JournalInternational Journal of Cancer
Volume124
Issue number9
DOIs
Publication statusPublished - 2009

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Pathology (Malmö) (013031000), Pathology, (Lund) (013030000)

Subject classification (UKÄ)

  • Cancer and Oncology

Keywords

  • tight junctions
  • claudin-4
  • prognostic biomarkers
  • breast cancers
  • tissue microarrays

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