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BioMed Research International
Volume 2014, Article ID 159765, 7 pages
http://dx.doi.org/10.1155/2014/159765
Research Article

New Biomarkers to Predict the Evolution of In Situ Breast Cancers

1Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy
2Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy
3Pathology Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy
4Breast Surgery Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy
5Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy
6Pathology Unit, Santa Maria delle Croci Hospital, 48010 Ravenna, Italy

Received 16 April 2014; Revised 21 July 2014; Accepted 23 July 2014; Published 26 August 2014

Academic Editor: Kapil Mehta

Copyright © 2014 S. Bravaccini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Genomic studies have shown that gene expression profiles are similar in in situ (CIS) and invasive breast cancers, suggesting that several biofunctional modifications of the transformation process occur before or during the development of CIS lesion. Methods. We investigated 3 biomarkers in 44 patients with CIS: TG2 (transglutaminase 2), HJURP (Holliday junction recognition protein), and HIF-1α (hypoxia inducible factor-1 alpha). Results. TG2 was more highly expressed than the other two markers and significantly more so in stromal than in tumor cells. HIF-1α evaluation showed a higher expression in both tumor and stromal cells in patients with relapsed G3 tumors, indicating a potential role of this marker in CIS evolution. A greater than sevenfold higher risk of relapse was observed in patients highly expressing HJURP in stroma and a tenfold higher recurrence risk was seen in those with a higher stromal HIF-1α expression. An important increase in risk accuracy (AUC 0.80) was obtained when HIF-1α and HJURP were evaluated together. Conclusions. Despite the limited number of relapsed patients, we formulated some hypotheses on the factors responsible for malignant evolution and recurrence which are now being tested in a large case series with a longer follow-up.