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

BMC Medicine

Marjanka K. Schmidt⁷  Marjo de Graauw^1,13  Montserrat García-Closas^3,30  Paul D. P. Pharoah⁵  Douglas F. Easton⁵  Georgia Chenevix-Trench²  Jenny Chang-Claude^1,10  Annegien Broeks^2,26  Bob van de Water^1,13  Carolien H. M. van Deurzen⁶  John W. M. Martens¹  Antoinette Hollestelle¹  Maartje J. Hooning¹  Bernd Holleczek^1,16  Volker Arndt^2,27  Katja Butterbach^2,27  Hermann Brenner^2,24  Daniel Visscher^2,25  Celine Vachon^2,28  Janet E. Olson^2,28  Fergus J. Couch^2,25  Kelly-Anne Phillips⁸  Jaana M. Hartikainen^1,11  Veli-Matti Kosma^1,11  Vesa Kataja^1,19  Arto Mannermaa^1,11  Jolanta Lissowska^2,20  Mark Sherman⁴  Jonine Figueroa^2,29  Hamid Raza Ali³  Elena Provenzano^1,17  Carl Blomqvist⁹  Kristiina Aittomäki⁹  Päivi Heikkilä⁹  Rainer Fagerholm^2,22  Jan H. M. Schellens^2,21  Gazinska Patrycja^1,15  Penny Coulson^3,30  Fiona M. Blows⁵  Ingrid Hofland^2,26  Joyce Sanders^2,23  Martine H. van Miltenburg^2,23  Heli Nevanlinna^2,22  Vincent T. H. B. M. Smit^1,14  Jelle Wesseling^1,18  Marcelo Sobral-Leite^1,12 

[1] Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands;Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia;Department of Pathology, University of Cambridge, Cambridge, UK;Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA;Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK;Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands;Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066, CX, The Netherlands;Department of Medicine, St Vincent’s Hospital, The University of Melbourne, Melbourne, Australia;University of Helsinki, Helsinki, Finland;Division of Cancer Epidemiology, Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany;Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland;Programa de Farmacologia, Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil;Division of Toxicology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands;Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands;Breakthrough Breast Cancer Centre, London, UK;Saarland Cancer Registry, Saarbrücken, Germany;Department of Histopathology, Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK;Division of Diagnostic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands;Jyväskylä Central Hospital, Jyväskylä, Finland;Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland;Department of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht, The Netherlands;Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland;Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands;Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany;Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA;Core Facility Molecular Pathology and Biobanking, Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands;Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany;Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA;Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA;Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK

关键词: BRCA1 and BRCA2 mutations;    Annexin A1;    Breast cancer;   

Others  :  1217706
DOI  :  10.1186/s12916-015-0392-6

 received in 2015-02-18, accepted in 2015-06-04,  发布年份 2015

【 摘 要 】

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 (HR _adj  = 1.35; 95 % CI = 1.05–1.73), but the association weakened after 10 years (HR _adj  = 1.13; 95 % CI = 0.91–1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HR _adj  = 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.

【 授权许可】

   
2015 Sobral-Leite et al.

【 图 表 】

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