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Perineural Invasion and Risk of Lethal Prostate Cancer
Division of Urology, McMaster University, Hamilton ON, Canada.
Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA, United States; Department of Pathology, Trinity College Dublin, Dublin, Ireland.
Harvard Medical School, Boston Massachusetts, United States.
Department of Epidemiology, Boston University School of Public Health, Boston MA, United States; Harvard T.H. Chan School of Public Health, Boston MA, United States.
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2017 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, no 5, 719-726 p.Article in journal (Refereed) Published
Abstract [en]

Background: Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that the presence of PNI in prostate cancer has been associated with cancer aggressiveness.

Methods: We investigated the association between PNI and lethal prostate cancer in untreated and treated prostate cancer cohorts: the Swedish Watchful Waiting Cohort of 615 men who underwent watchful waiting, and the U.S. Health Professionals Follow-Up Study of 849 men treated with radical prostatectomy. One pathologist performed a standardized histopathologic review assessing PNI and Gleason grade. Patients were followed from diagnosis until metastasis or death.

Results: The prevalence ofPNI was7% and 44% in the untreated and treated cohorts, respectively. PNI was more common in high Gleason grade tumors in both cohorts. PNI was associated with enhanced tumor angiogenesis, but not tumor proliferation or apoptosis. In the Swedish study, PNI was associated with lethal prostate cancer [OR 7.4; 95% confidence interval (CI), 3.6-16.6; P < 0.001]. A positive, although not statistically significant, associationpersisted after adjustment for age, Gleason grade, and tumor volume (OR 1.9; 95% CI, 0.8-5.1; P = 0.17). In the U.S. study, PNI predicted lethal prostate cancer independent of clinical factors (HR 1.8; 95% CI, 1.0, 3.3; P = 0.04).

Conclusions: These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness. Impact: Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis. (C) 2017 AACR.

Place, publisher, year, edition, pages
American Association for Cancer Research Inc. , 2017. Vol. 26, no 5, 719-726 p.
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-57864DOI: 10.1158/1055-9965.EPI-16-0237ISI: 000400524700008PubMedID: 28062398Scopus ID: 2-s2.0-85015798340OAI: oai:DiVA.org:oru-57864DiVA: diva2:1104003
Funder
Swedish Cancer Society, CAN 2006/1341Swedish Research Council, 2009-7309
Note

Funding Agencies:

NIH  PO1 CA055075  CA141298  CA13389  UM1 CA167552 

U.S. Army Prostate Cancer Research Program Idea Development Award  PC060389 

DF/HCC Prostate SPORE Career Development Award  NIH/NCI P50 CA90381 

Prostate Cancer Foundation Young Investigator Awards

Royal Physiographic Society in Lund, Sweden

Available from: 2017-05-31 Created: 2017-05-31 Last updated: 2017-09-06Bibliographically approved

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