Abstract
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.
Highlights
Metastasis to bone is a common feature in advanced prostate cancer (PCa) patients
E main aim of this study was to investigate the putative association among the presence of prostate cancer cells, de ned 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 positron emission tomography (PET)/computed tomography (CT) analysis
E 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 5years of diagnosis, and the uptake of 18F-choline evaluated by PET/CT analysis
Summary
Metastasis to bone is a common feature in advanced prostate cancer (PCa) patients. PCa is one of the most frequent cancer in men and represents a great public health problem, with a total of 265,000 new diagnosis every year in both Europe and United States of America [1]. The mechanisms responsible for the formation of prostate cancer metastasis to bone are complex and certainly involve both osteoclasts and osteoblasts activity [6]. In this context, the binary classification between osteoblastic and osteolytic lesions represents two extremes of a continuum which involves dysregulation of the normal bone remodeling process and which is yet to be fully understood. A detailed characterization of the osteoblastic-osteolytic spectrum and of premetastatic tumour cells could pave the way for both the identification of early markers for bone metastasis and of novel drug targets to improve quality of life of patients with advanced prostate cancer
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