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Increased claudin-4...
Increased claudin-4 expression is associated with poor prognosis and high tumour grade in breast cancer
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Lanigan, Fiona (author)
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McKiernan, Eadaoin (author)
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Brennan, Donal J. (author)
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Hegarty, Shauna (author)
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Millikan, Robert C. (author)
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McBryan, Jean (author)
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- Jirström, Karin (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Landberg, Göran (author)
- Lund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups
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Martin, Finian (author)
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Duffy, Michael J. (author)
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Gallagher, William M. (author)
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(creator_code:org_t)
- Wiley, 2009
- 2009
- English.
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:9, s. 2088-2097
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- tight junctions
- claudin-4
- prognostic biomarkers
- breast cancers
- tissue microarrays
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Lanigan, Fiona
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McKiernan, Eadao ...
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Brennan, Donal J ...
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Hegarty, Shauna
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Millikan, Robert ...
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McBryan, Jean
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show more...
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Jirström, Karin
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Landberg, Göran
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Martin, Finian
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Duffy, Michael J ...
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Gallagher, Willi ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Lund University