AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 2011;3(1):100-113

Original Article
Iron-binding proteins and C-reactive protein in nipple aspirate fluids:  
role of Iron-driven inflammation in breast cancer microenvironment?

Ferdinando Mannello , Gaetana A. Tonti, Patrizia Simone, Daniela Ligi and  Virginia Medda

Department of Biomolecular Sciences, Section of Clinical Biochemistry, Unit of Cell Biology, University “Carlo Bo”,
Urbino, Italy

Received October 25, 2010; Accepted October, 2010; Epub October, Published January 1, 2011

Abstract: Breast cancer, a worldwide disease with increasing incidence, develops from ductal/lobular epithelium.
Nipple aspirate fluid (NAF), secreted from the breast ducts and lobules, can be analyzed to assess metabolic
activity in breast microenvironment. Premalignant and malignant cell alterations may produce biochemical
signals that deliver inflammatory proteins to the site. C-reactive protein (CRP), acute-phase protein considered a
prognostic marker of inflammation, is frequently over-expressed in invasive breast carcinomas. Starting from the
evidence that soluble and cell-bound iron binding protein Ferritin (FTN) and Transferrin (TRF) are crucially
involved in breast inflammation and cancer, the aim of the present study is to analyze in NAF (a ductal fluid
mirroring the breast microenvironment noninvasively collected from healthy and proven breast cancer affected
women, n=38), the concentrations of CRP, FTN and TRF through high sensitive immunoassays. We analysed
also serum (n=35) and milk samples (n=20) from healthy subjects. The mean level of CRP in Cancer NAF was
significantly higher than in NoCancer NAF (P < 0.0001), especially in postmenopausal patients.  Moreover, in
Cancer NAF we detected higher levels of TRF and FTN respect to NoCancer NAF (P<0.001). A highly significant
positive correlation between FTN and CRP content (Y= 2322x + 6.196, r2 = 0.651, P<0.0001)  was found. These
data may support the involvement of inflammation and deregulation of iron homeostasis in breast cancer etio-
pathogenesis. The significant accumulation of CRP in NAF in conjunction to the disruption of iron homeostasis
may help to identify women at higher breast cancer risk. (AJTR1010003).

Keywords: Breast cancer, ferritin, iron, inflammation, nipple aspirate fluid, transferrin

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Address all correspondence to:
Ferdinando Mannello, PhD
Dept of Biomolecular Sciences
Section of Clin Biochem & Cell Biol
University “Carlo Bo” of Urbino
61029 Urbino (PU), Italy.
Tel +39-0722-351479,  Fax +39-0722-322370
E-mail:
ferdinando.mannello@uniurb.it