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Contains fulltext : 136616.pdf (Publisher’s version ) (Open Access) PURPOSE: Urinary biomarker tests for diagnosing prostate cancer have gained considerable interest. Urine is a complex mixture that can be subfractionated. We evaluated 2 urinary fractions that contain nucleic acids, ie cell pellets and exosomes. The influence of digital rectal examination before urine collection was also studied and the prostate cancer specific biomarkers PCA3 and TMPRSS2-ERG were assayed. MATERIALS AND METHODS: Urine samples were prospectively obtained before and after digital rectal examination from 30 men scheduled for prostate biopsy. Cell pellet and exosomes were isolated and used for biomarker analysis. Analytical and diagnostic performance was tested using the Student t-test and ROC curves. RESULTS: Unlike the exosome fraction, urinary sediment gene expression analysis was compromised by amorphous precipitation in 10% of all specimens. Digital rectal examination resulted in increased mRNA levels in each fraction. This was particularly relevant for the exosomal fraction since after digital rectal examination the number of samples decreased in which cancer specific markers were below the analytical detection limit. Biomarker diagnostic performance was comparable to that in large clinical studies. In exosomes the biomarkers had to be normalized for prostate specific antigen mRNA while cell pellet absolute PCA3 levels had diagnostic value. CONCLUSIONS: Exosomes have characteristics that enable them to serve as a stable substrate for biomarker analysis. Thus, digital rectal examination enhances the analytical performance of biomarker analysis in exosomes and cell pellets. The diagnostic performance of biomarkers in exosomes differs from that of cell pellets. Clinical usefulness must be prospectively assessed in larger clinical cohorts.

A 52-year-old male presented with an asymptomatic palpable mass of the right testicle. Ultrasound confirmed the presence of a testicular tumour and a hemicastration was performed. None of the testis cancer-related tumour markers were elevated and histological findings revealed a neuroendocrine carcinoma, possibly a metastasis from another primary site. The radiological findings showed a lesion in the lung, and a positron emission tomography (PET)-scan was made. The PET scan revealed an increased fluorodeoxyglucose (FDG) uptake in the pulmonary lesion. It also showed lymphatic and hepatic metastases. The patient had no complaints besides a palpable testicular mass and was diagnosed with a cT1aN3M1b neuroendocrine carcinoma of the lower left field of the lung, stage IV. To our knowledge, the presentation of testicular metastasis of a neuroendocrine carcinoma of the lung has not been described in the literature. No curative options were available and the patient is being treated with salvage chemotherapy.