Intraprostatic inflammation is positively associated with serum PSA in men with PSA <4 ng ml(-1), normal DRE and negative for prostate cancer.
BACKGROUND
Biopsies performed for elevated serum PSA often show inflammatory infiltrates. However, the influence of intraprostatic inflammation on serum PSA in men without biopsy indication and negative for prostate cancer has not been described in detail.


METHODS
We studied 224 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT) who underwent end-of-study biopsy per trial protocol, had PSA <4 ng ml(-1), normal digital rectal examination and a biopsy negative for cancer. We analyzed data from hematoxylin and eosin-stained slides containing a mean of three biopsy cores. Inflammation measures included the extent (percentage of tissue area with inflammation) and intensity (product of scores for extent and grade) of total, acute and chronic inflammation in the entire tissue area examined, and by tissue compartment. We calculated median measures of inflammation by prebiopsy serum PSA tertile (>0 to ≤0.8, >0.8 to ≤1.5 and >1.5 to <4.0 ng ml(-1)). We estimated the association between percentage of tissue area with inflammation and natural logarithm of PSA using linear regression adjusting for age at biopsy.


RESULTS
Median percentage of tissue area with inflammation increased from 2 to 5 to 9.5% across PSA tertiles (P-trend <0.0001). For every 5% increase in tissue area with inflammation, log PSA increased by 0.061 ng ml(-1) (P=0.0002). Median extent and intensity scores increased across PSA tertiles in luminal and intraepithelial compartments for acute inflammation and in stromal and intraepithelial compartments for chronic inflammation (all P-trend ≤0.05).


CONCLUSIONS
In men without clinical suspicion of prostate cancer, greater overall inflammation, luminal and intraepithelial acute inflammation and stromal and intraepithelial chronic inflammation were associated with higher serum PSA.
1] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA [2] Department of Urology and the James Buchanan Brady Urological Institute, Baltimore, MD, USA [3] Department of Urology, City Hospital Triemli of Zurich, Zurich, Switzerland [4] Horten Center for Patient Related Research and Knowledge Transfer, University of Zurich, Zurich, Switzerland.
M H
MH
Umbehr
1] Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA [2] Department of Pathology, Amasya University Sabuncuoglu Serefeddin Training and Research Hospital, Amasya, Turkey.
B
B
Gurel
1] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA [2] Department of Urology, School of Medicine, Tampere University Hospital, University of Tampere, Tampere, Finland.
T J
TJ
Murtola
Division of Public Health Sciences and the Alvin J Siteman Cancer Center, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
S
S
Sutcliffe
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
S B
SB
Peskoe
SWOG Statistical Center, and the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
C M
CM
Tangen
SWOG Statistical Center, and the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
P J
PJ
Goodman
Department of Urology, University of Texas Health Sciences Center San Antonio, San Antonio, TX, USA.
I M
IM
Thompson
Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
S M
SM
Lippman
University of Colorado Denver School of Medicine, Aurora, CO, USA.
M S
MS
Lucia
Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
H L
HL
Parnes
1] Department of Urology and the James Buchanan Brady Urological Institute, Baltimore, MD, USA [2] Department of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA [3] Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
C G
CG
Drake
1] Department of Urology and the James Buchanan Brady Urological Institute, Baltimore, MD, USA [2] Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
W G
WG
Nelson
1] Department of Urology and the James Buchanan Brady Urological Institute, Baltimore, MD, USA [2] Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA [3] Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
A M
AM
De Marzo
1] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA [2] Department of Urology and the James Buchanan Brady Urological Institute, Baltimore, MD, USA [3] Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
E A
EA
Platz
D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology*; D012307:Risk Factors
D017430:Prostate-Specific Antigen