Open AccessClaudin‐2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences
Author(s) -
Kimbung Siker,
Kovács Anikó,
Bendahl Pär-Ola,
Malmström Per,
Fernö Mårten,
Hatschek Thomas,
Hedenfalk Ingrid
Publication year - 2014
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2013.10.002
Subject(s) - medicine , breast cancer , cohort , oncology , metastasis , proportional hazards model , cancer , metastatic breast cancer , immunohistochemistry , biomarker , primary tumor , stage (stratigraphy) , pathology , biology , biochemistry , paleontology
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.