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Intraprostatic inflammation is positively associated with serum PSA in men with PSA <4 ng ml−1, normal DRE and negative for prostate cancer

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Abstract

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.

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Acknowledgements

This work was funded by the National Cancer Institute, National Institutes of Health P01 CA108964 (to IM Thompson, Project 4 EA Platz) and P50 CA58236 (to WG Nelson). The PCPT is funded by Public Health Service Grants U10 CA37429 and UM1 CA182883 (to IM Thompson/CM Tangen) from the National Cancer Institute. In addition, Dr De Marzo is the recipient of the Virginia and Warren Schwerin Scholar Award and Dr Platz is the recipient of the Beth W and A Ross Myers Scholar Award, both from the Patrick C Walsh Prostate Cancer Research Fund. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Author notes

  1. A M De Marzo and E A Platz: Co-senior authors.

Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    M H Umbehr, T J Murtola, S B Peskoe & E A Platz

  2. Department of Urology and the James Buchanan Brady Urological Institute, Baltimore, MD, USA

    M H Umbehr, C G Drake, W G Nelson, A M De Marzo & E A Platz

  3. Department of Urology, City Hospital Triemli of Zurich, Zurich, Switzerland

    M H Umbehr

  4. Horten Center for Patient Related Research and Knowledge Transfer, University of Zurich, Zurich, Switzerland

    M H Umbehr

  5. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    B Gurel & A M De Marzo

  6. Department of Pathology, Amasya University Sabuncuoglu Serefeddin Training and Research Hospital, Amasya, Turkey

    B Gurel

  7. Department of Urology, School of Medicine, Tampere University Hospital, University of Tampere, Tampere, Finland

    T J Murtola

  8. 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 Sutcliffe

  9. and the Division of Public Health Sciences, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    C M Tangen & P J Goodman

  10. Department of Urology, University of Texas Health Sciences Center San Antonio, San Antonio, TX, USA

    I M Thompson

  11. Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA

    S M Lippman

  12. University of Colorado Denver School of Medicine, Aurora, CO, USA

    M S Lucia

  13. Division of Cancer Prevention, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    H L Parnes

  14. Department of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    C G Drake

  15. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

    C G Drake, W G Nelson, A M De Marzo & E A Platz

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  1. M H Umbehr
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  2. B Gurel
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  3. T J Murtola
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  4. S Sutcliffe
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  5. S B Peskoe
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  6. C M Tangen
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  7. P J Goodman
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  8. I M Thompson
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  9. S M Lippman
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  10. M S Lucia
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  11. H L Parnes
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  12. C G Drake
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  13. W G Nelson
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  14. A M De Marzo
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  15. E A Platz
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Corresponding author

Correspondence to M H Umbehr.

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Umbehr, M., Gurel, B., Murtola, T. et al. Intraprostatic inflammation is positively associated with serum PSA in men with PSA <4 ng ml−1, normal DRE and negative for prostate cancer. Prostate Cancer Prostatic Dis 18, 264–269 (2015). https://doi.org/10.1038/pcan.2015.19

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  • DOI: https://doi.org/10.1038/pcan.2015.19

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