Annexin A1 expression in a pooled breast cancer series: association with tumor subtypes and prognosisReportar como inadecuado




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BMC Medicine

, 13:156

First Online: 02 July 2015Received: 18 February 2015Accepted: 04 June 2015DOI: 10.1186-s12916-015-0392-6

Cite this article as: Sobral-Leite, M., Wesseling, J., Smit, V.T.H.B.M. et al. BMC Med 2015 13: 156. doi:10.1186-s12916-015-0392-6

Abstract

BackgroundAnnexin 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.

MethodsClinical-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.

ResultsThe 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.

ConclusionsANXA1 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.

KeywordsBreast cancer Annexin A1 BRCA1 and BRCA2 mutations AbbreviationsANXA1Annexin A1

BCACBreast Cancer Association Consortium

BCSSBreast cancer-specific survival

CC1Cell Conditioning 1

CFMPBCore Facility Molecular Pathology and Biobanking

ChaK1Channel kinase 1

CIConfidence interval

DMFSDistant metastasis-free survival

EGFREpidermal growth factor receptor

EMTEpithelial-mesenchymal transition

EREstrogen receptor

HRHazard ratio

HUCHHelsinki University Central Hospital

IHCImmunohistochemistry

IRInsulin receptor

OROdds ratio

OSOverall survival

PKAProtein kinase A

PKCProtein kinase C

PRProgesterone receptor

TMATissue microarray

TNTriple negative

Electronic supplementary materialThe online version of this article doi:10.1186-s12916-015-0392-6 contains supplementary material, which is available to authorized users.

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