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

Lanigan, Fiona; McKiernan, Eadaoin; Brennan, Donal J.; Hegarty, Shauna; Millikan, Robert C.; McBryan, Jean; Jirström, Karin LU ; Landberg, Göran LU ; Martin, Finian and Duffy, Michael J., et al. (2009) In International Journal of Cancer 124(9). p.2088-2097
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... (More)
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. (Less)
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published
subject
keywords
tight junctions, claudin-4, prognostic biomarkers, breast cancers, tissue microarrays
in
International Journal of Cancer
volume
124
issue
9
pages
2088 - 2097
publisher
John Wiley & Sons
external identifiers
  • wos:000264647600012
  • scopus:63449095110
ISSN
0020-7136
DOI
10.1002/ijc.24159
language
English
LU publication?
yes
id
84810c78-5caf-4ab8-beac-f8be39d51990 (old id 1401047)
date added to LUP
2009-06-15 12:37:46
date last changed
2017-09-03 03:48:36
@article{84810c78-5caf-4ab8-beac-f8be39d51990,
  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.},
  author       = {Lanigan, Fiona and McKiernan, Eadaoin and Brennan, Donal J. and Hegarty, Shauna and Millikan, Robert C. and McBryan, Jean and Jirström, Karin and Landberg, Göran and Martin, Finian and Duffy, Michael J. and Gallagher, William M.},
  issn         = {0020-7136},
  keyword      = {tight junctions,claudin-4,prognostic biomarkers,breast cancers,tissue microarrays},
  language     = {eng},
  number       = {9},
  pages        = {2088--2097},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Increased claudin-4 expression is associated with poor prognosis and high tumour grade in breast cancer},
  url          = {http://dx.doi.org/10.1002/ijc.24159},
  volume       = {124},
  year         = {2009},
}