Characterization of the Peri-Membrane Fluorescence Phenomenon Allowing the Detection of Urothelial Tumor Cells in Urine

SIMPLE SUMMARY: To detect bladder cancer (BC), urinary cytology and cystoscopy are the primary diagnostic tests used. Urine cytology is non-invasive, easy to collect, with medium sensitivity and high specificity. It is an effective way to detect high-grade BC, but it is less effective on low-grade BC because the rate of equivocal results is much higher, making them difficult to detect. Despite the implementation of new diagnostics, urinary cytology and cystoscopy remain the gold standard. Instead of looking for new diagnostics, one of the new research areas is the improvement of urinary cytology. Recently, the fluorescent properties of plasma membranes of urothelial tumor cells, called peri-membrane fluorescence, found in urinary cytology have been shown to be useful in improving the early detection of BC. The main objective of this study was to characterize the peri-membrane fluorescence allowing the detection of urothelial tumor cells in urine. ABSTRACT: Urine cytology is non-invasive, easy to collect, with medium sensitivity and a high specificity. It is an effective way to detect high-grade bladder cancer (BC), but it is less effective on low-grade BC because the rate of equivocal results is much higher. Recently, the fluorescent properties of plasma membranes of urothelial tumor cells (UTC) found in urine cytology have been shown to be useful in improving the early detection of BC. This phenomenon is called peri-membrane fluorescence (PMF). Based on previous studies that have identified the PMF on UTCs, the main objective was to characterize this phenomenon. For this study, a software was specially created to quantify the PMF of all tested cells and different treatments performed. PMF was not found to be a morphological and discriminating feature of UTCs, all cells in shape and not from urine show PMF. We were able to highlight the crucial role of plasma membrane integrity in the maintenance of PMF. Finally, it was found that the induction of a strong cellular stress induced a decrease in PMF, mimicking what was observed in non-tumor cells collected from urine. These results suggest that PMF is found in cells able to resist this stress, such as tumor cells.