Calcifications in prostate cancer: An active phenomenon mediated by epithelial cells with osteoblast‐phenotype

Contrast Media & Molecular Imaging

Urbano

Bonfiglio

et al. 2018

Self Cite

The main aim of this study was to investigate the putative association among the presence of prostate cancer cells, defined as prostate osteoblast-like cells (POLCs), and showing the expression of typical morphological and molecular characteristics of osteoblasts, the development of bone metastasis within 5 years of diagnosis, and the uptake of 18F-choline evaluated by PET/CT analysis. To this end, prostate biopsies (n = 110) were collected comprising 44 benign lesions and 66 malignant lesions. Malignant lesions were further subdivided into two groups: biopsies from patients that had clinical evidence of bone metastasis (BM+, n = 23) and biopsies from patients that did not have clinical evidence of bone metastasis within 5 years (BM−, n = 43). Paraffin serial sections were obtained from each specimen to perform histological classifications and immunohistochemical (IHC) analysis. Small fragments of tissue were used to perform ultrastructural and microanalytical investigations. IHC demonstrated the expression of markers of epithelial-to-mesenchymal transition (VIM), bone mineralization, and osteoblastic differentiation (BMP-2, PTX-3, RUNX2, RANKL, and VDR) in prostate lesions characterized by the presence of calcium-phosphate microcalcifications and high metastatic potential. Ultrastructural studies revealed the presence of prostate cancer cells with osteoblast phenotype close to microcalcifications. Noteworthy, PET/CT analysis showed higher uptake of 18F-choline in BM+ lesions with high positivity (≥300/500 cells) for RUNX2 and/or RANKL immunostaining. Although these data require further investigations about the molecular mechanisms of POLCs generation and role in bone metastasis, our study can open new and interesting prospective in the management of prostate cancer patients. The presence of POLCs along with prostate microcalcifications may become negative prognostic markers of the occurrence of bone metastases.

Section: Resultssupporting

confidence: 56%

Prostate Osteoblast-Like Cells: A Reliable Prognostic Marker of Bone Metastasis in Prostate Cancer Patients

Contrast Media & Molecular Imaging

Urbano

Bonfiglio

et al. 2018

Self Cite

“…In light of this, it is possible to speculate an increase of the uptake of sestamibi in breast cancers with a high number of BOLCs due to the increase of the high-transmembrane-potential mitochondria during the formation of microcalcifications made of HA that are generally produced by the BOLCs themselves. In agreement with this evidence, ultrastructural observations demonstrated the presence of several mitochondria, both in osteoblast-like cells and real osteoblasts during calcification production [10,23,24]. Therefore, BSGI with [ 99 mTc]Tc-Sestamibi could be used to stratify breast cancer patients based on the risk of developing bone metastases given the presence of a high number of BOLCs.…”

Section: Discussionsupporting

confidence: 65%

Breast-Specific Gamma Imaging with [99mTc]Tc-Sestamibi: An In Vivo Analysis for Early Identification of Breast Cancer Lesions Expressing Bone Biomarkers

Urbano

Russo

et al. 2020

JCM

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The main purpose of this pilot investigation was to evaluate the possible relationship among [99mTc]Tc-Sestamibi uptake, the presence of breast osteoblast-like cells, and the expression of molecules involved in bone metabolism, such as estrogen receptor, bone morphogenetic proteins-2, and PTX3. To this end, forty consecutive breast cancer patients who underwent both breast-specific gamma imaging with [99mTc]Tc-Sestamibi and breast bioptic procedure were retrospectively enrolled. From each diagnostic paraffin block collected in the study, histological diagnosis, immunohistochemical investigations, and energy dispersive X-ray microanalysis were performed. Our data highlight the possible use of breast-specific gamma imaging with [99mTc]Tc-Sestamibi for the early detection of breast cancer lesions expressing bone biomarkers in the presence of breast osteoblast-like cells. Specifically, we show a linear association among sestamibi uptake, the presence of breast osteoblast-like cells, and the expression of estrogen receptor, bone morphogenetics proteins-2, and PTX3. Notably, we also observed an increase of [99mTc]Tc-Sestamibi in breast cancer lesions with magnesium-substituted hydroxyapatite. In conclusion, in this pilot study we evaluated data from the nuclear medicine unit and anatomic pathology department on breast cancer osteotropism, identifying a new possible interpretation of Breast Specific Gamma Imaging with [99mTc]Tc-Sestamibi analysis.

“…Interestingly, Energy Dispersive X-Ray (EDX) -microanalysis revealed that Mg-HAp calcifications appeared in conjunction with malignant lesions exclusively [7]. Recent discoveries in the field of the biology of breast and prostate calcifications demonstrated the presence of cells capable to produce calcified crystals [7,9]. In addition, our and other studies showed that only the complex form of calcification (HA and Mg-HAp) were produced by these cells (osteoblast-like cells) [7].…”

Section: Introductionmentioning

confidence: 65%

Radiological, Histological and Chemical Analysis of Breast Microcalcifications: Diagnostic Value and Biological Significance

Bonfiglio

J Mammary Gland Biol Neoplasia

Toschi

et al. 2018

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Classification of mammary microcalcifications is based on radiological and histological characteristics that are routinely evaluated during the diagnostic path for the identification of breast cancer, or in patients at risk of developing breast cancer. The main aim of this study was to explore the relationship between the imaging parameters most commonly used for the study of mammary microcalcifications and the corresponding histological and chemical properties. To this end, we matched the radiographic characteristics of microcalcifications to breast lesion type, histology of microcalcifications and elemental composition of microcalcifications as obtained by energy dispersive x ray (EDX)-microanalysis. In addition, we investigated the properties of breast cancer microenvironment, under the hypothesis that microcalcification formation could result from a mineralization process similar to that occurring during bone osteogenesis. In this context, breast lesions with and without microcalcifications were compared in terms of the expression of the main molecules detected during bone mineralization (BMP-2, BMP-4, PTX3, RANKL OPN and RUNX2). Our data indicate that microcalcifications classified by mammography as "casting type" are prevalently made of hydroxyapatite magnesium substituted and are associated with breast cancer types with the poorest prognosis. Moreover, breast cancer cells close to microcalcifications expressed higher levels of bone mineralization markers as compared to cells found in breast lesions without microcalcifications. Notably, breast lesions with microcalcifications were characterized by the presence of breast-osteoblast-like cells. In depth studies of microcalcifications characteristics could support a new interpretation about the genesis of ectopic calcification in mammary tissue. Candidating this phenomenon as an integral part of the tumorigenic process therefore has the potential to improve the clinical management of patients early during their diagnostic path.