Repository logo
 

Annexin A1 expression in a pooled breast cancer series: association with tumor subtypes and prognosis.


Change log

Authors

Sobral-Leite, Marcelo 
Wesseling, Jelle 
Smit, Vincent THBM 
Nevanlinna, Heli 
van Miltenburg, Martine H 

Abstract

BACKGROUND: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients. METHODS: Clinical-pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model. RESULTS: The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6 % versus 12.4 %, respectively; P <0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HRadj = 1.35; 95 % CI = 1.05-1.73), but the association weakened after 10 years (HRadj = 1.13; 95 % CI = 0.91-1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45). CONCLUSIONS: ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases.

Description

Keywords

Adult, Annexin A1, Biomarkers, Tumor, Breast Neoplasms, Female, Genes, BRCA1, Genes, BRCA2, Genetic Predisposition to Disease, Humans, Immunohistochemistry, Middle Aged, Mutation, Prognosis

Journal Title

BMC Med

Conference Name

Journal ISSN

1741-7015
1741-7015

Volume Title

13

Publisher

Springer Science and Business Media LLC
Sponsorship
National Cancer Institute (R01CA128978)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research UK (12014)
Cancer Research UK (10118)
Cancer Research UK (16563)
Cancer Research Uk (None)
Cancer Research UK [C1287/A10118, C1287/A12014, C490/A10124 C490/A10119 and C490/A16561], the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge; BIHR Biomedical Research Centre at the University of Cambridge; Dutch Cancer Society [grants NKI 2007-3839; 2009 4363; DDHK 2004-3124, DDHK 2009-4318]; Baden Württemberg Ministry of Science, Research and Arts, Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation, Special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, Australia National Breast Cancer Foundation, National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, the Cancer Foundation of Western Australia, NIH grants [CA128978, CA116167, CA176785], NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], the Breast Cancer Research Foundation, the David F. and Margaret T. Grohne Family Foundation, the Ting Tsung and Wei Fong Chao Foundation, Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA and CAPES Foundation. KAP is supported by a National Breast Cancer Foundation Practitioner Fellowship.