ABSTRACT
INTRODUCTION: We sought to determine if prostate cancer (PCa) is associated with worse lower urinary tract symptoms (LUTS) than matched benign prostates, with attention to cancer characteristics, in a contemporary cohort. METHODS: Using a single-institution database (January 1, 2009-June 30, 2013), men diagnosed with PCa on biopsy and controls with negative biopsies were matched 1:1 on age, prostate volume, and a propensity score predicting the probability of PCa diagnosis. International Prostate Symptom Score (IPSS) was compared between PCa cases and controls using paired statistics, stratifying on grade, cancer volume, stage, and D'Amico risk group. Sensitivity analyses were performed separately, repeating the match for high-grade, high-volume, and high-stage cancers only, and excluding users of benign prostatic hyperplasia medications. RESULTS: In our cohort of 1330 men (665 with PCa), there were 284 (42.7%) Gleason 6 cancers (Grade Group 1), 315 (47.4%) Gleason 7 cancers (Grade Group 2-3), and 66 (9.9%) Gleason 8-10 cancers (Grade Group 4-5). There was no difference in IPSS between PCa cases (median 6.5, interquartile range [IQR] 3-12) and benign controls (median 7, IQR 3-13; p=0.34). Subgroup analyses based on cancer grade, volume, or stage, showed no significant differences in IPSS between men with and without PCa, except among men with cT2b-cT4 PC (median 9, IQR 5-16) vs. matched benign counterparts (median 8, IQR 3-12; p=0.03). Sensitivity analyses supported these findings. CONCLUSIONS: Modern PCa does not appear to be associated with worse LUTS compared to benign prostates of the same size. Outlet obstruction is likely a late event in the natural history of PCa. This has implications for timely PCa detection, which should ideally be prior to the onset of LUTS.
ABSTRACT
Protein interacting specifically with Tc10, PIST, is a Golgi-associated sorting protein involved in regulating cell-surface targeting of plasma membrane receptors. The present study provides the first comprehensive description of PIST distribution in the mammalian central nervous system and of its subcellular localization by immunocytochemistry. PIST is distributed widely throughout the neuraxis, predominantly associated with neuronal cell bodies and dendrites. In hippocampal neurons, in vitro and in situ, PIST displayed a patchy subcellular distribution in an area surrounding the nucleus and extending into one of the major dendrites. By colocalization with the trans-Golgi marker TGN38, we were able to show that PIST is associated largely but not exclusively with the trans-Golgi network in central neurons. High or moderate to high levels of PIST-like immunoreactivity were found in cortical areas, in particular in layer V of the neocortex. The motor cortex was most strongly labeled. Also, the piriform and insular cortices displayed strong PIST labeling. In the hippocampus, CA2 but not CA1 or CA3 pyramidal cells displayed strong PIST-labeling, extending into their apical dendrites. In the thalamus, ventrolateral and laterodorsal nuclei were most strongly stained, whereas in the hypothalamus the supraoptic nucleus stood out with strong immunoreactivity. Strikingly, in the brainstem all cranial nerve motor nuclei were PIST-positive at varying levels, which is in keeping with the prominent expression of PIST in forebrain motor areas. This selective distribution of PIST suggests that the protein serves distinctive roles in specific neuronal populations, establishing functionally distinct zones, for instance, in the hippocampus.
