Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer.Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression. During this process, cells lose their epithelial characteristics and acquire mesenchymal features. Increasing evidences indicate that EMT promotes prostate cancer metastatic progression and it is closely correlated with increased stemness and drug resistance.In this review, we discuss the main molecular events that directly or indirectly govern the EMT program in prostate cancer, in order to better define the role and the mechanisms underlying this process in prostate cancer progression and therapeutic resistance.

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis.

The metastatic process is the most serious cause of cancer death. Norepinephrine, secreted in chronic stress conditions, stimulates the motility of breast and colon cells through β-adrenergic receptor. On these bases, we examined its possible role in metastasis formation and development in vitro and in vivo. Treatments with norepinephrine (β2-adrenoreceptor agonist) in mice xenografted with human DU145 prostate cancer cells increased the metastatic potential of these cells. Specifically, we showed that treatment of mice with norepinephrine induced a significant increase of the migratory activity of cancer cells in a concentration-dependent manner and that this process was blocked by propanolol (β-adrenergic antagonist). Mice treated with norepinephrine, displayed an increased number of metastatic foci of DU145 cells in inguinal lymph nodes and also showed an increased expression of MMP2 and MMP9 in tumor samples compared to controls. Moreover, we demonstrated that propanolol induced in norepinephrine treated DU145 cells a E-cadherin finger-like membrane protrusions driven by vimentin remodeling. Altogether these data suggest that β2-AR plays an important role in prostate cancer metastasis formation and that the treatment with antagonist propanolol, could represents an interesting tool to control this process in cells overexpressing β2AR.

BackgroundSolitary fibrous tumor is an uncommon soft tissue neoplasm with intermediate biological behavior, which rarely metastasizes. Malignant solitary fibrous tumor, although not clearly defined, is rarely described in the prostate. The present case is characterized by some peculiarities if compared with previously reported cases of prostatic malignant solitary fibrous tumor. Firstly, it does not show a homogeneous morphology: part of the neoplasm (about 50%) showed the features of a conventional solitary fibrous tumor, while the remaining part showed the features of a malignant solitary fibrous tumor. In addition, the case is the first malignant solitary fibrous tumor reaching a huge diameter of 20 cm and replacing all prostatic parenchyma. Interestingly, normal prostatic parenchyma was observed on left-lobe trans-rectal needle-core biopsies, but was totally absent in surgical specimen. Since radical prostatectomy was carried out about 4 months after the biopsies, such discordant data may suggest exceedingly rapid growth of the neoplasm.Case presentationWe report a case of a 62-year-old male, presented at medical observation for urinary retention, constipation and an enlarged prostate gland. A trans-rectal prostatic biopsy showed a low-grade spindle cell neoplasm. Histopathological examination of the prostatectomy specimen showed patternless architecture with hypocellular and hypercellular areas and hemangiopericytoma-like vessels. In some fields the neoplasm was characterized by a high mitotic index and evident cellular atypia. Immunohistochemically, neoplastic cells were positive for CD34, bcl2, CD99, STAT6 and partially for PgR. The neoplasm was diagnosed as a malignant solitary fibrous tumor.ConclusionsThe differential diagnosis of spindle cells tumors arising in the prostrate is broad and includes lesions of epithelial and mesenchymal origin, primary prostatic lesions such as stromal tumors of uncertain malignant potential and stromal sarcoma, as well as anatomically ubiquitous soft tissue neoplasms. Solitary fibrous tumors should be considered in cases of prostatic tumors with a spindled morphology, but malignancy in such tumors is extremely rare in the prostate. A review of literature showed only four additional cases. Because of the unpredictable biological behavior and the possibility of recurrence, a long-term clinical and instrumental follow-up is recommended.

Background High-risk human papillomavirus (HR-HPV) is notoriously associated with tumor progression in a broad spectrum of malignancies. Detection of HR-HPV is clinically important in the management of HPV-related carcinomas, particularly in cervical cancer and oropharyngeal squamous cell carcinoma (OPSCC). Several methods for HPV detection are currently available including Polymerase chain reaction (PCR)-based techniques, DNA in situ hybridization (ISH), RNA ISH, and p16 immunohistochemistry (IHC). Currently, the guidelines for HPV detection in cervical carcinoma are available, while no clear consensus has not yet been reached on the gold standard for HPV testing in OPSCC. Multimodality testing could help to reliably identify patients with transcriptionally active high-risk HPV-positive. Methods We propose a multiplex approach carrying out HPV RNA ISH and p16 IHC on the same slide to detect simultaneously HPV E6/E7 transcripts and p16INK4a overexpression. We tested this assay in two different series one of the cervical cancers with p16-positive, as control, and the other of oropharyngeal squamous cell carcinomas with blind p16 status. Results The multiplex HPV RNA ISH /p16 IHC results in the series both of the cervical cancers and the oral-oropharyngeal cancers were fully concordant with the previous results achieved through the classic p16 IHC and HPV RNA scope carried out on two different slides. Conclusions Our results suggesting several advantages of this technical approach, namely an easy interpretation fully in the light field, the feasibility in formalin-fixed paraffin-embedded tissue sections, complete automation and a potential wide spreadable for routine testing in several clinical laboratories.