Abstract Autophagy is a conserved evolutionary process that allows cells to maintain macromolecular synthesis and energy homeostasis during starvation and stressful conditions. We prospectively evaluated the relationship between autophagy and prostatic inflammation in a series of transurethral prostatic resection samples. Inflammatory infiltrates were defined according to the standardized classification of chronic prostatitis of the National Institute of Health. The inflammatory score (IS score) was calculated. High IS score was defined as ≥7. Each sample was stained for anti-LC3B and for anti-P62/SQSTM1 and scored. High p62 or LC3B percentage was defined as >25%, whereas low was defined as <25% of cells with dots.We analyzed 94 specimens. Overall, 18/94 (19%) showed no sign of prostatic inflammation, whereas 76/94 (81%) presented inflammatory infiltrates. Inflammation was mild in 61/76 (80%), moderate/severe in 15/76 (20%). Patients with high p62 percentage were 62/94 (66%) while 32 (34%) showed low p62 percentage. Patients with high LC3B percentage were 37/94 (39%) while 57(61%) showed low LC3B percentage. Overall 42/94 (44%) patients presented a high p62 percentage and concomitant a low LC3B percentage. IS score was significantly higher in patients with a with high p62 percentage (median IS 7 (6/8) vs 5 (3/7); p= 0.04) and in patients with a low LC3B percentage (median IS 7 (6/8) vs 5 (3/7); p= 0.004) when compared to patients with a low p62 percentage or a high LC3B percentage respectively. On multivariate analysis, p62 (OR: 10.1, 95%CI: 2.6-38.6; p= 0,001) and LC3B expression (OR: 0.319; 95%CI: 0.112-0.907; p= 0.032) were independent predictors of a high IS.Here we present the first evidence of autophagy deregulation in prostatic inflammation. These results raise many questions about the mechanisms mediating the autophagy dysfunction and the links to prostatic inflammation that need to be addressed.

Autophagy deactivation is associated with severe prostatic inflammation in patients with lower urinary tract symptoms and benign prostatic hyperplasia / DE NUNZIO, Cosimo; Giglio, Simona; Stoppacciaro, Antonella; Gacci, Mauro; Cirombella, Roberto; Luciani, Emidio; Tubaro, Andrea; Vecchione, Andrea. - In: ONCOTARGET. - ISSN 1949-2553. - STAMPA. - (2017), pp. 50904-50910. [10.18632/oncotarget.15144]

Autophagy deactivation is associated with severe prostatic inflammation in patients with lower urinary tract symptoms and benign prostatic hyperplasia

DE NUNZIO, Cosimo;GIGLIO, SIMONA;STOPPACCIARO, ANTONELLA;CIROMBELLA, Roberto;LUCIANI, Emidio;TUBARO, ANDREA;VECCHIONE, ANDREA
2017

Abstract

Abstract Autophagy is a conserved evolutionary process that allows cells to maintain macromolecular synthesis and energy homeostasis during starvation and stressful conditions. We prospectively evaluated the relationship between autophagy and prostatic inflammation in a series of transurethral prostatic resection samples. Inflammatory infiltrates were defined according to the standardized classification of chronic prostatitis of the National Institute of Health. The inflammatory score (IS score) was calculated. High IS score was defined as ≥7. Each sample was stained for anti-LC3B and for anti-P62/SQSTM1 and scored. High p62 or LC3B percentage was defined as >25%, whereas low was defined as <25% of cells with dots.We analyzed 94 specimens. Overall, 18/94 (19%) showed no sign of prostatic inflammation, whereas 76/94 (81%) presented inflammatory infiltrates. Inflammation was mild in 61/76 (80%), moderate/severe in 15/76 (20%). Patients with high p62 percentage were 62/94 (66%) while 32 (34%) showed low p62 percentage. Patients with high LC3B percentage were 37/94 (39%) while 57(61%) showed low LC3B percentage. Overall 42/94 (44%) patients presented a high p62 percentage and concomitant a low LC3B percentage. IS score was significantly higher in patients with a with high p62 percentage (median IS 7 (6/8) vs 5 (3/7); p= 0.04) and in patients with a low LC3B percentage (median IS 7 (6/8) vs 5 (3/7); p= 0.004) when compared to patients with a low p62 percentage or a high LC3B percentage respectively. On multivariate analysis, p62 (OR: 10.1, 95%CI: 2.6-38.6; p= 0,001) and LC3B expression (OR: 0.319; 95%CI: 0.112-0.907; p= 0.032) were independent predictors of a high IS.Here we present the first evidence of autophagy deregulation in prostatic inflammation. These results raise many questions about the mechanisms mediating the autophagy dysfunction and the links to prostatic inflammation that need to be addressed.
BPH; LUTS; autophagy; inflammation; prostate
01 Pubblicazione su rivista::01a Articolo in rivista
Autophagy deactivation is associated with severe prostatic inflammation in patients with lower urinary tract symptoms and benign prostatic hyperplasia / DE NUNZIO, Cosimo; Giglio, Simona; Stoppacciaro, Antonella; Gacci, Mauro; Cirombella, Roberto; Luciani, Emidio; Tubaro, Andrea; Vecchione, Andrea. - In: ONCOTARGET. - ISSN 1949-2553. - STAMPA. - (2017), pp. 50904-50910. [10.18632/oncotarget.15144]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/956253
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