Comparison of conventional transrectal ultrasound, magnetic resonance imaging, and micro-ultrasound for visualizing prostate cancer in an active surveillance population: A feasibility study.

INTRODUCTION: Active surveillance monitoring of prostate cancer is unique in that most patients have low-grade disease that is not well-visualized by any common imaging technique. High-resolution (29 MHz) micro-ultrasound is a new, real-time modality that has been demonstrated to be sensitive to significant prostate cancer and effective for biopsy targeting. This study compares micro-ultrasound imaging with magnetic resonance imaging (MRI) and conventional ultrasound for visualizing prostate cancer in active surveillance. METHODS: Nine patients on active surveillance were imaged with multiparametric (mp) MRI prior to biopsy. During the biopsy procedure, imaging and target identification was first performed using conventional ultrasound, then using micro-ultrasound. The mpMRI report was then unblinded and used to determine cognitive fusion targets. Using micro-ultrasound, biopsy samples were taken from targets in each modality, plus 12 systematic samples. RESULTS: mpMRI and micro-ultrasound both demonstrated superior sensitivity to Gleason sum 7 or higher cancer compared to conventional ultrasound (p=0.02 McNemar's test). Micro-ultrasound detected 89% of clinically significant cancer, compared to 56% for mpMRI. CONCLUSIONS: Micro-ultrasound may provide similar sensitivity to clinically significant prostate cancer as mpMRI and visualize all significant mpMRI targets. Unlike mpMRI, micro-ultrasound is performed in the office, in real-time during the biopsy procedure, and so is expected to maintain the cost-effectiveness of conventional ultrasound. Larger studies are needed before these results may be applied in a clinical setting.

Dysregulated expression of cell surface glycoprotein CDCP1 in prostate cancer.

CUB-domain-containing protein 1 (CDCP1) is a trans-membrane protein regulator of cell adhesion with a potent pro-migratory function in tumors. Given that proteolytic cleavage of the ectodomain correlates with outside-in oncogenic signaling, we characterized glycosylation in the context of cellular processing and expression of CDCP1 in prostate cancer. We detected 135 kDa full-length and proteolytic processed 70 kDa species in a panel of PCa cell models. The relative expression of full-length CDCP1 correlated with the metastatic potential of syngeneic cell models and an increase in surface membrane expression of CDCP1 was observed in tumor compared to adjacent normal prostate tissues. We demonstrated that glycosylation of CDCP1 is a prerequisite for protein stability and plasma membrane localization, and that the expression level and extent of N-glycosylation of CDCP1 correlated with metastatic status. Interestingly, complex N-linked glycans with sialic acid chains were restricted to the N-terminal half of the ectodomain and absent in the truncated species. Characterization of the extracellular expression of CDCP1 identified novel circulating forms and revealed that extracellular vesicles provide additional processing pathways. Employing immunoaffinity mass spectrometry, we detected elevated levels of circulating CDCP1 in patient urine with high-risk disease. Our results establish that differential glycosylation, cell surface presentation and extracellular expression of CDCP1 are hallmarks of PCa progression.