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Mol Oncol. 2014 Feb;8(1):119-28. doi: 10.1016/j.molonc.2013.10.002. Epub 2013 Oct 14.

Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences.

Author information

  • 1Division of Oncology, Department of Clinical Sciences, Lund, Lund University, Sweden; CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden.
  • 2Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • 3Division of Oncology, Department of Clinical Sciences, Lund, Lund University, Sweden.
  • 4Division of Oncology, Department of Clinical Sciences, Lund, Lund University, Sweden; Skåne Department of Oncology, Skåne University Hospital, Lund, Sweden.
  • 5Department of Oncology and Pathology, Karolinska Institutet and Karolinska University Hospital, Sweden.
  • 6Division of Oncology, Department of Clinical Sciences, Lund, Lund University, Sweden; CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden. Electronic address: Ingrid.Hedenfalk@med.lu.se.

Abstract

BACKGROUND:

Predicting any future metastatic site of early-stage breast cancer is important as it significantly influences the prognosis of advanced disease. This study aimed at investigating the potential of claudin-2, over-expressed in breast cancer liver metastases, as a biomarker for predicting liver metastatic propensity in primary breast cancer.

METHODS:

Claudin-2 expression was analyzed in two independent cohorts. Cohort 1 included 304 women with metastatic breast cancer diagnosed between 2002 and 2007, while cohort 2 included 237 premenopausal women with early-stage node-negative breast cancer diagnosed between 1991 and 1994. Global transcriptional profiling of fine-needle aspirates from metastases was performed, followed by immunohistochemical analyses in archival primary tumor tissue. Associations between claudin-2 expression and relapse site were assessed by univariable and multivariable Cox regression models including conventional prognostic factors. Two-sided statistical tests were used.

RESULTS:

CLDN2 was significantly up-regulated (P < 0.001) in liver metastases compared to other metastatic sites. Claudin-2 protein was more frequently expressed in primary tumors from patients who subsequently developed liver metastases (P = 0.02) and high expression was associated with a shorter metastasis-free interval (cohort 1, HR = 1.4, 95% CI = 1.0-1.9; cohort 2, HR = 2.2, 95% CI = 1.3-3.5). Specifically, a significantly shorter interval between primary tumor diagnosis and liver-specific recurrence was observed among patients with high levels of claudin-2 expression in the primary tumor (cohort 1, HR = 2.3, 95% CI = 1.3-3.9).

CONCLUSION:

These results suggest a novel role for claudin-2 as a prognostic biomarker with the ability to predict not only the likelihood of a breast cancer recurrence, but more interestingly, the liver metastatic potential of the primary tumor.

Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

BCSS; Breast cancer; CI; CLDN2; Claudin-2; ER; HR; IHC; LNM; LiMFS; Liver metastasis; OR; PR; Prognostic biomarker; RFS; TMA; breast cancer specific survival; claudin-2 mRNA; confidence interval; estrogen receptor; hazard ratio; immunohistochemistry; liver metastasis-free survival; lymph node metastasis; odds ratio; progesterone receptor; relapse-free survival; tissue microarray

PMID:
24287398
[PubMed - in process]
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