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

Molecular Oncology - Tập 8 Số 1 - Trang 119-128 - 2014
Siker Kimbung1, Anikó Kovács2, Pär‐Ola Bendahl1, Per Malmström3, Mårten Fernö1, Thomas Hatschek4, Ingrid Hedenfalk1
1Division of Oncology, Department of Clinical Sciences, Lund, Lund University, Sweden
2Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
3Skåne Department of Oncology, Skåne University Hospital, Lund, Sweden
4Department of Oncology and Pathology, Karolinska Institutet and Karolinska University hospital, Sweden

Tóm tắt

BackgroundPredicting 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.MethodsClaudin‐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).ConclusionThese 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.

Từ khóa


Tài liệu tham khảo

Bos M., 1997, PD153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptor activation and inhibits growth of cancer cells in a receptor number-dependent manner, Clin. Cancer Res., 3, 2099

10.1038/nature08021

10.1080/02841860310004724

10.1038/onc.2011.43

10.1002/ijc.24131

10.1002/jcp.20189

10.1083/jcb.153.2.263

10.1200/JCO.1988.6.1.89

10.1007/s10549-011-1619-7

10.1007/s10549-011-1880-9

10.1093/nar/gkn923

10.1038/nprot.2008.211

10.1016/j.ejso.2006.09.005

10.1016/S1535-6108(03)00132-6

10.1200/JCO.2009.25.9820

10.1111/j.1365-2559.2008.03052.x

10.1038/modpathol.2009.167

10.1093/annonc/mdn424

10.1200/JCO.2001.19.7.2010

10.1016/j.ctrv.2004.09.007

10.1038/nature03799

10.1038/nm0806-875

10.1007/s10549-005-9117-4

10.1002/mc.20485

10.1186/bcr2635

10.1046/j.1523-1755.2002.00479.x

10.1369/jhc.7A7211.2007

10.1152/ajpcell.00274.2007

10.1634/theoncologist.8-3-241

10.1158/0008-5472.CAN-07-5644

10.1016/j.humpath.2004.09.015

10.1111/j.1365-2559.2005.02127.x

10.1023/A:1006308619659

10.1056/NEJMra0801289

10.1007/s10585-010-9357-5

10.1038/onc.2010.518

10.1128/MCB.00299-12

10.1158/1541-7786.MCR-06-0071

The R Project for Statistical Computing. www.r-project.org.

10.1038/labinvest.2008.78

10.1073/pnas.2634067100

10.3816/CBC.2010.n.009

Thông tin
Thông tin xuất bản

Molecular Oncology

Tập 8 Số 1

119-128

Thông tin tác giả