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this context, the expression of BMP-2 and PTX3 in BM+ lesions can provide a scientific rationale for BOLCs
development and microcalcifications formation. Also, it is known that both BMP-2 and PTX3 are involved
in the EMT phenomenon. Thus, it is possible to speculate that these molecules have role both in BOLCs
generation that in the production of HA or MgHAp crystals by the BOLCs themselves.

In conclusion, results here reported highlighted the possible use of breast microcalcifications as a negative
prognostic marker of bone metastatic diseases. In particular, the association between elemental composition
of breast microcalcifications and the formation of bone lesions can lay the foundation for the development of
new in vivo diagnostic tools based on the analysis of microcalcifications and capable to predict the formation
of bone metastasis. In this scenario, the in vivo analysis of elemental composition of microcalcifications by
RAMAN spectroscopy could improve the clinical armamentarium available for the diagnosis and stadiation
of breast cancer.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception and design of the study and performed data analysis and
interpretation: Bonfiglio R, Scimeca M, Bonanno E
Performed data acquisition and performed administrative, technical, and material supports: Polidori A,
Nazzaro C, De Silva G

Availability of data and materials
The data used to support the findings of this study are included within the article. Further details can be
made available upon request.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Our study protocol was approved by independent ethical committee. Experimental procedures were carried
out according to The Code of Ethics of the World Medical Association (Declaration of Helsinki). Specimens
were handled and carried out in accordance with the approved guidelines.

Consent for publication
Not applicable.

Copyright
©The Author(s) 2019.

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