Microcalcifications Drive Breast Cancer Occurrence and Development by Macrophage-Mediated Epithelial to Mesenchymal Transition.

BACKGROUND: This study aims to investigate: (a) the putative association between the presence of microcalcifications and the expression of both epithelial-to-mesenchymal transition and bone biomarkers, (b) the role of microcalcifications in the breast osteoblast-like cells (BOLCs) formation, and (c) the association between microcalcification composition and breast cancer progression. METHODS: We collected 174 biopsies on which we performed immunohistochemical and ultrastructural analysis. In vitro experiments were performed to demonstrate the relationship among microcalcification, BOLCs development, and breast cancer occurrence. Ex vivo investigations demonstrated the significant increase of breast osteoblast-like cells in breast lesions with microcalcifications with respect to those without microcalcifications. RESULTS: In vitro data displayed that in the presence of calcium oxalate and activated monocytes, breast cancer cells undergo epithelial to mesenchymal transition. Also, in this condition, cells acquired an osteoblast phenotype, thus producing hydroxyapatite. To further confirm in vitro data, we studied 15 benign lesions with microcalcification from patients that developed a malignant condition in the same breast quadrant. Immunohistochemical analysis showed macrophages' polarization in benign lesions with calcium oxalate. CONCLUSIONS: Altogether, our data shed new light about the role of microcalcifications in breast cancer occurrence and progression.

Negative prognostic value of intra-ductal fat infiltrate in breast cancer.

BACKGROUND: Recent studies showed a correlation between Body Mass Index and both breast cancer occurrence and progression. Nevertheless, no study reported an accurate evaluation of intra-ductal fat infiltrate. Therefore, the main aim of this study was to evaluate the putative association between intra-ductal fat infiltrate (IDFi) and breast cancer subtypes by using digital pathology. METHODS: We retrospectively collected 220 breast biopsies. Paraffin serial sections were used for haematoxylin and eosin staining and immunohistochemical evaluation of the following markers: estrogen receptor (ER), progesterone receptor (PR), Ki67 and c-erb2. Three haematoxylin and eosin sections for each paraffin block were digitalized. Digital slides were used to evaluate the areas of IDFi. Five randomized areas were evaluated for each slide. By using GraphPad software IDFi areas was correlated with a) breast cancer histotype, b) presence of microcalcifications and c) biomarkers expression. RESULTS: Breast biopsies were classified as follow: 20 normal breast, 50 benign lesions, and 150 malignant lesions (85 ductal in situ carcinomas; 65 ductal infiltrating carcinomas). Statistical analysis showed a significant increase of IDFi in malignant lesions as compared to both normal breast and benign lesions. We noted higher IDFi in breast ductal carcinomas as compared to lobular lesions. Significant differences were observed between breast lesions with microcalcifications respect to lesions without calcifications. Noteworthy, we also found a positive association between IDFi and the expression of both ER and Ki67. CONCLUSION: Results of our study highlighted the possible role of fat in breast cancer progression suggesting a negative prognostic value of IDFi.