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Prostate Cancer

The Microbiome of the Prostate Tumor Microenvironment

Ilaria Cavarretta

a , y

, Roberto Ferrarese

b ,

y

, Walter Cazzaniga

a ,

Diego Saita

c ,

Roberta Luciano`

d ,

Elisa R. Ceresola

e ,

Irene Locatelli

a ,

Laura Visconti

f

[2_TD$DIFF]

,

Giovanni Lavorgna

a ,

Alberto Briganti

a , b ,

Manuela Nebuloni

g

[3_TD$DIFF]

,

Claudio Doglioni

b , d ,

Massimo Clementi

b , c

[2_TD$DIFF]

,

Francesco Montorsi

a , b ,

Filippo Canducci

e

[1_TD$DIFF]

, f

[4_TD$DIFF]

, y , * ,

Andrea Salonia

a , b ,

y

a

Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy;

b

Universita` Vita-Salute San Raffaele, Milan, Italy;

c

Microbiology Unit, IRCCS Ospedale San Raffaele, Milan, Italy;

d

[5_TD$DIFF]

Pathology Unit, IRCCS Ospedale San Raffaele, Milan, Italy;

e

Department of Biotechnology and

Life Sciences, University of Insubria, Varese, Italy;

f

Human Virology Unit, IRCCS Ospedale San Raffaele, Milan, Italy;

g

Pathology Unit, Department of

Biomedical and Clinical Sciences, L. Sacco Hospital, Universita` degli Studi di Milano, Milan, Italy

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 6 2 5 – 6 3 1

ava ilable at

www.sciencedirect.com

journal homepage:

www.eu ropeanurology.com

Article info

Article history:

Accepted March 21, 2017

Associate Editor:

Christian Gratzke

Keywords:

Microbiome

Propionibacterium acnes

Prostate cancer

Tumor microenvironment

Staphylococcus

spp

.

Streptococcus

spp

.

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www.eu-acme.org/ europeanurology

to read and

answer questions on-line.

The EU-ACME credits will

then be attributed

automatically.

Abstract

Background:

The advent of molecular-based methods of identification and characteri-

zation of complex microbial populations has led to a new era of microbial discovery. A

detailed and comprehensive analysis of the microbial ecosystem of the pathologic and

healthy prostate tissues has not been yet reported.

Objectives:

To characterize the microbiome possibly associated to the pathologic pros-

tate microenvironment.

Design, setting, and participants:

The microbiome profile of tumor, peri-tumor, and

nontumor tissues was assessed on 16 radical prostatectomy-specimens.

Outcome measurements and statistical analysis:

Microbiome analysis was assessed by

massive ultradeep pyrosequencing. Bacteria load was expressed as a percentage of the

total number of bacteria. The statistical significance of differences among specimen-

groups was tested with Friedman’s test (Dunn posthoc test) and Wilcoxon rank-sum

test.

Results and limitations:

Three phyla, six classes, nine orders, 14 families, and 11 genera

were above the set threshold value of 1%, respectively. Significant differences in specific

microbial populations among tumor/peri-tumor and nontumor prostate specimens

were observed at certain taxonomic levels. Among genera,

Propionibacterium

spp

.

were the most abundant.

Staphylococcus

spp

.

were more represented in the tumor/

peri-tumor tissues (

p

<

0.05). The restricted number of specimens represents a poten-

tial limitation.

Conclusions:

The prostate contains a plethora of bacteria, which set themselves within

the gland with a distribution dependent on the nature of the tissue, thus suggesting a

possible pathophysiological correlation between the composition of the local microbial

niche and the presence of the tumor itself. Future studies will help to clarify the role of

these specific bacteria and their potential to be exploited as new biomarkers.

Patient summary:

The pathological prostate is populated by specific microbial popula-

tions, whose distribution varies according to the nature of the tissue. This finding opens

interesting perspectives for the identification of novel therapeutic approaches and

biomarkers.

#

2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

y

These authors contributed equally to this paper.

* Corresponding author. Microbiology Unit, IRCCS Ospedale San Raffaele, Via Olgettina 60, Milan

20132, Italy. Tel. +39 02 2643 4284; Fax: +39 02 2643 4284.

E-mail address:

Canducci.filippo@gmail.com

(F. Canducci).

http://dx.doi.org/10.1016/j.eururo.2017.03.029

0302-2838/

#

2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.