title: Perineural Invasion and Risk of Lethal Prostate Cancer.
abstract: 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 of PNI was 7% 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, association persisted 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.Cancer Epidemiol Biomarkers Prev; 26(5); 719-26. ©2017 AACR.
authors.affiliation: Division of Urology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Piotr
authors.initials: P
authors.lastname: Zareba
authors.affiliation: Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.|Department of Pathology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Richard
authors.initials: R
authors.lastname: Flavin
authors.affiliation: Harvard Medical School, Boston, Massachusetts.
authors.forename: Masis
authors.initials: M
authors.lastname: Isikbay
authors.affiliation: Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.|Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Rider
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Travis A
authors.initials: TA
authors.lastname: Gerke
authors.affiliation: Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.|Department of Pathology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Finn
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Clinical Epidemiology Unit, Department of Medicine, Solna, Stockholm, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pettersson
authors.affiliation: Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Giunchi
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Unger
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Tinianow
authors.affiliation: Department of Urology, Örebro University Hospital, Örebro, Sweden.|School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Swen-Olof
authors.initials: SO
authors.lastname: Andersson
authors.affiliation: Department of Urology, Örebro University Hospital, Örebro, Sweden.|School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Ove
authors.initials: O
authors.lastname: Andrén
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Katja
authors.initials: K
authors.lastname: Fall
authors.affiliation: Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.|Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts. lmucci@hsph.harvard.edu.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.|Division of Public Health Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010525:Peripheral Nerves / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*