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

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Author

  • 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
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Summary, in English

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.

Publishing year

2009

Language

English

Pages

2088-2097

Publication/Series

International Journal of Cancer

Volume

124

Issue

9

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Cancer and Oncology

Keywords

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

Status

Published

Research group

  • Pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 0020-7136