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.

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These results indicate that the new biotin-DOTA conjugate may be a suitable candidate for pretargeting trials.

Background In this study, we investigated the relationship between the expression of the main in situ markers of breast cancer and the presence of breast osteoblast-like cells (BOLCs). Methods We collected 100 breast biopsies. Serial paraffin sections were obtained from each biopsy to perform histological classifications and immunohistochemical analyses (RUNX2, RANKL, vimentin, TGFβ, Ki67, CD44, ER, PR and HER2). Results Linear regression analysis showed a positive and significant correlation between the number of BOLCs and the expression of EMT-related markers (vimentin and TGFβ), Ki67 and ER. Conversely, we observed an inverse correlation between the number of CD44-positive breast cancer cells and the BOLCs. No significant differences were observed between the number of BOLCs and the HER2 scores. Conclusions Morphological and molecular characterisation of BOLCs can lay the foundations towards understanding the biological basis of the formation of breast microcalcifications, and breast cancer metastasis to bone. The data here reported may be useful for the identification of breast lesions with high potential to develop bone metastasis.

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Clinical PET/CT is a well-known useful tool for the in vivo noninvasive quantitative imaging of physiologic and pathologic processes [1]. Actually, the key role of PET/CT in cancer staging and therapeutic responses to personalized treatments is well established; it is an essential imaging modality not only in oncology but also in neuroscience and in all the applications of molecular imaging. In recent years, there have been multiple advances in PET/CT scanners: new hardware, software, and acquisition methods to improve image quality [2]. Nevertheless, till now PET detectors have been mainly based on photomultiplier tubes (PMT), which have well-known advantages but also several limitations that affect, in particular, small lesions detection [3]. The introduction of digital detectors in PET/CT scanners may represent an important improvement in this diagnostic technology [4].In this issue of EJNMMI, Lopez-Mora et al.[5] present a step forward in this field, comparing image quality and lesion detection capability between a digital (d) and an analog (a) PET/CT system in 100 patients with oncologic diseases who were prospectively included in this study. The patients consecutively underwent a single day, dual imaging protocol (d and aPET/CT) after a i.v. injection of either FDG or fluorocholine. The first PET/CT was performed 60 min after the i.v. injection of the radiopharmaceutical, and the second imaging dataset was acquired with a mean time delay of 50 ± 14 min. In the patients referred for an initial assessment (n = 58), the dPET/CT was performed first, while in the patients who were evaluated for therapy monitoring, the aPET/CT was firstly acquired. Three nuclear medicine physicians evaluated image quality using a 4-point scale (−1, poor to 2, excellent) and detection capability by counting the number of lesions with increased uptake of the radiopharmaceutical. In 54% of patients, dPET/CT allowed a better image quality than aPET/ CT; in the remaining 46 patients, image quality did not significantly differ between both devices. Regarding lesion detection capability, dPET/CT was able to visualize lesions in three patients in whom the a system resulted negative; moreover, in 19 out of 80 cases which were positive at aPET/CT imaging, the dPET/CT detected more lesions. In these 22 patients, all the lesions visualized only by means of the dPET/CT were < 1 cm in size: eight were in the lungs, eight in lymph-nodes, six in the liver, four in bones, and one in seminal vesicles, in the breasts and in the skin, respectively. It is worth noting that dPET/CT changed staging in 32% of these patients (7 out of 22).In the same group of 100 oncological patients, another recent study was conducted to assess whether dPET/CT impact on the quantification of SUVmax in target lesions (the most metabolically active in each case) and in reference regions (liver and mediastinal blood pool) in comparison to aPET/CT [6]. The findings of this paper indicate that SUVmax of the target lesions and mediastinal blood pool measured by the d system w...

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The immune system plays an important role in the defense against neoplastic disease and immune responses show temporal changes related to circadian variations of antibodies, total lymphocytes in the peripheral blood and cell mediated immune responses. In this study we evaluate. lymphocyte subpopulations and interleukin-2 (IL-2) serum levels in peripheral blood samples collected at four-hour intervals for 24-hours starting at 06.00h from ten healthy subjects aged 65-79 years (mean age ± S.E. 67.28 ±3.1l) and from ten subjects suffering from untreated non small cell lung cancer aged 65-78 years (mean age ±S.E. 68.57 ±1.81). Areas under the curve, mean diurnal levels (mean of 06. 00-10.00-14.00 h) and mean nocturnal levels (mean of 18.00-22.00-02.00 h) were calculated, and the presence of circadian rhythmicity was evaluate. When we compared AVC values there was a decrease in CD8bright (T suppressor subset) and an increase in CD16 (natural killer cells) and of IL-2 serum levels in cancer patients. When we compared mean diurnal levels, CD8 (T suppressor/cytotoxic subset) and CD8hright levels were lower, and CD16 levels were higher in cancer patients. When we compared mean nocturnal levels, CD16 and CD25 (T and B activated lymphocytes with expression of the a chain ofIL-2 receptor) levels were higher, while CD8, CD8bright, CD20 (total B-cells), TcRdl (epitope of the constant domain of d chain of T-cell receptor 1) and dTcSl (epitope of the variable domain of d chain of T-cell receptorl) levels were lower in cancer patients. A clear circadian rhythm was validated for the time-qualified changes in CD4, CD20, HLA-DR with acrophase at night, and CD8, CD8 bright, CD8 dim, CDI6, TcRdl and dTcSl with acrophase in the morning in the control group. A clear circadian rhythm was validated for the time-qualified changes in CD4 with acrophase at night, in the group of cancer patients. Results obtained in our study show that lung cancer is associated with anomalies of proportion and circadian variations of lymphocyte subsets that must be considered when adoptive immunotherapy has to be planned.Immune response is important in the natural history of neoplastic disease and lymphocytes are an essential component of this biological host reaction. Peripheral blood lymphocytes show that circadian variations of specific subpopulations (1-10), and abnormalities in the proportions of various lymphocyte subsets have been found in a number of tumors (11-13). Strategies to enhan.ce immunological response, above all cellular immunity, in oncologic patients, rely on biological response modifiers and adoptive immunotherapy. It is important to identify immunological alterations in cancer patients in order to evaluate immunomodulatory effects. The aim of this study is to evaluate alterations in the immune system function expressed as modifications in the 24-hour pattern ofIL-2 and 1ymphocyte subsets changes in patients suffering from lung cancer.