ABSTRACT
BACKGROUND: Data are lacking for the accuracy of computed tomography (CT) in measuring prostate size, which can streamline care and prevent invasive procedures. We evaluate agreement and intra/inter-observer variability in prostate sizing between CT and magnetic resonance imaging (MRI) planimetry for a wide range of gland sizes. METHODS: We retrospectively reviewed 700 patients who underwent MRI fusion biopsy at a single institution and identified 89 patients that had a CT within 2 years of the MRI. Six reviewers from different training levels were categorized as student, resident, or attending and each measured prostate size on CT by the prolate ellipse method. Bland-Altman analysis determined the degree of agreement between CT and MRI. Inter- and intra-observer reliability was calculated for CT. RESULTS: Mean CT volume was higher than MRI volume in the < 60 g group (51.5 g vs. 44.5 g, p = 0.004), but not in the ≥ 60 g group (101 g vs. 100 g, p = 0.458). The bias for overestimation of prostate volume by CT was 4.1 g across prostate volumes, but the proportional agreement between modalities improved with size. The Pearson correlation coefficient between CT/MRI and inter/intra-rater reliability for CT increased in the ≥ 60 g vs. the < 60 g group for all training levels. CONCLUSIONS: Our data show that there is greater clinical utility for prostate size estimation by CT than previously established, particularly for larger glands where accurate size estimation may influence therapeutic decisions. In larger glands, prostate size estimation by CT is also reproducible across various training levels.
ABSTRACT
Heat shock protein-90 (Hsp90) chaperone machinery is involved in the stability and activity of its client proteins. The chaperone function of Hsp90 is regulated by co-chaperones and post-translational modifications. Although structural evidence exists for Hsp90 interaction with clients, our understanding of the impact of Hsp90 chaperone function toward client activity in cells remains elusive. Here, we dissect the impact of recently identified higher eukaryotic co-chaperones, FNIP1/2 (FNIPs) and Tsc1, toward Hsp90 client activity. Our data show that Tsc1 and FNIP2 form mutually exclusive complexes with FNIP1, and that unlike Tsc1, FNIP1/2 interact with the catalytic residue of Hsp90. Functionally, these co-chaperone complexes increase the affinity of the steroid hormone receptors glucocorticoid receptor and estrogen receptor to their ligands in vivo. We provide a model for the responsiveness of the steroid hormone receptor activation upon ligand binding as a consequence of their association with specific Hsp90:co-chaperone subpopulations.
