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The prognostic relevance of FOXA1 and Nestin expression in breast cancer metastases: a retrospective study of 164 cases during a 10-year period (2004-2014)

Journal article
Authors Shahin De Lara
Jenny Nyqvist
Elisabeth Werner Rönnerman
Khalil Helou
E. K. Sarenmalm
Zakaria Einbeigi
Per Karlsson
Toshima Z Parris
Anikó Kovács
Published in Bmc Cancer
Volume 19
ISSN 1471-2407
Publication year 2019
Published at Institute of Clinical Sciences, Department of Oncology
Sahlgrenska Cancer Center
Institute of Biomedicine, Department of Pathology
Language en
Keywords FOXA1, Nestin, GATA3, Breast cancer metastases, Immunohistochemistry, box protein a1, neoadjuvant chemotherapy, marker, association, subtype
Subject categories Cancer and Oncology


BackgroundCurrent prognostic markers cannot adequately predict the clinical outcome of breast cancer patients. Therefore, additional biomarkers need to be included in routine immune panels. FOXA1 was a significant predictor of favorable outcome in primary breast cancer, while Nestin expression is preferentially found in triple-negative tumors with increased rate of nodal metastases, and reduced survival. No studies have investigated the prognostic value of FOXA1 and Nestin expression in breast cancer metastases.MethodsBreast cancer metastases (n=164) from various anatomical sites were retrospectively analyzed by immunohistochemistry for FOXA1, Nestin and GATA3 expression. Cox regression analysis assessed the prognostic value of FOXA1 and Nestin expression.ResultsIn breast cancer metastases, FOXA1 expression was associated with Nestin-negativity, GATA3-positivity, ER-positivity, HER2-positivity and non-triple-negative status (P<0.05). In contrast, Nestin expression was associated with FOXA1-negative, GATA3-negative, ER-negative, and triple-negative metastases (P<0.05). Univariate Cox regression analysis showed FOXA1 expression was predictive of overall survival (OS, P=0.00048) and metastasis-free survival (DMFS, P=0.0011), as well as, distant metastasis-free survival in ER-positive patients (P=0.036) and overall survival in ER-negative patients (P=0.024). Multivariate analysis confirmed the significance of FOXA1 for both survival endpoints in metastatic breast cancer patients (OS, P=0.0033; DMFS, P=0.015).ConclusionsIn our study, FOXA1 was expressed mostly in ER-positive breast cancer metastases. Expression of Nestin was related to triple-negative metastases, where brain was the most frequent metastatic site. These findings highlight the clinical utility of FOXA1 and Nestin expression and warrant their inclusion in routine immunohistochemical panels for breast carcinoma.

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