Claudin‐2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences. Issue 1 (14th October 2013)

• Record Type: Journal Article
• Authors: Kimbung, Siker; Kovács, Anikó; Bendahl, Pär-Ola; Malmström, Per; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid
• Is Part Of: Molecular oncology. Volume 8:Issue 1(2014:Jan.)
• Page Start: 119
• Page End: 128
• Publication Date: 2013-10-14
• Subjects: Breast cancer -- Liver metastasis -- Claudin‐2 -- Prognostic biomarker; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1016/j.molonc.2013.10.002
• Languages: English
• ISSNs: 1574-7891

Abstract

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. Highlights: Breast cancer patients with hepatic recurrences have an inferior outcome. CLDN2 is significantly over‐expressed in liver compared to other metastases. CLDN2 expression is frequent in primary tumors from patients with liver metastases. CLDN2 expression is prognostic of a shorter relapse‐free interval. CLDN2 expression is an independent predictor for early liver metastases.