Perineural Invasion and Risk of Lethal Prostate Cancer

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. We investigated the association between PNI and lethal prostate cancer i...

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Published in:	Cancer epidemiology, biomarkers & prevention Vol. 26; no. 5; p. 719
Main Authors:	Zareba, Piotr, Flavin, Richard, Isikbay, Masis, Rider, Jennifer R, Gerke, Travis A, Finn, Stephen, Pettersson, Andreas, Giunchi, Francesca, Unger, Robert H, Tinianow, Alex M, Andersson, Swen-Olof, Andrén, Ove, Fall, Katja, Fiorentino, Michelangelo, Mucci, Lorelei A
Format:	Journal Article
Language:	English
Published:	United States 01.05.2017
Subjects:	Adult Aged Cohort Studies Humans Male Middle Aged Neoplasm Grading - methods Neoplasm Invasiveness - pathology Peripheral Nerves - pathology Prostatic Neoplasms - pathology
ISSN:	1538-7755, 1538-7755
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Abstract	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. 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. 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; < 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; = 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; =0.04). These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness. Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis. .
AbstractList	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.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. 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. 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. 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; < 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; = 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; =0.04). These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness. Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis. .
Author	Andersson, Swen-Olof Mucci, Lorelei A Giunchi, Francesca Rider, Jennifer R Finn, Stephen Tinianow, Alex M Flavin, Richard Fall, Katja Unger, Robert H Andrén, Ove Isikbay, Masis Pettersson, Andreas Gerke, Travis A Zareba, Piotr Fiorentino, Michelangelo
Author_xml	– sequence: 1 givenname: Piotr surname: Zareba fullname: Zareba, Piotr organization: Division of Urology, McMaster University, Hamilton, Ontario, Canada – sequence: 2 givenname: Richard surname: Flavin fullname: Flavin, Richard organization: Department of Pathology, Trinity College Dublin, Dublin, Ireland – sequence: 3 givenname: Masis surname: Isikbay fullname: Isikbay, Masis organization: Harvard Medical School, Boston, Massachusetts – sequence: 4 givenname: Jennifer R surname: Rider fullname: Rider, Jennifer R organization: Harvard T.H. Chan School of Public Health, Boston, Massachusetts – sequence: 5 givenname: Travis A surname: Gerke fullname: Gerke, Travis A organization: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida – sequence: 6 givenname: Stephen surname: Finn fullname: Finn, Stephen organization: Department of Pathology, Trinity College Dublin, Dublin, Ireland – sequence: 7 givenname: Andreas surname: Pettersson fullname: Pettersson, Andreas organization: Clinical Epidemiology Unit, Department of Medicine, Solna, Stockholm, Sweden – sequence: 8 givenname: Francesca surname: Giunchi fullname: Giunchi, Francesca organization: Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Bologna, Italy – sequence: 9 givenname: Robert H surname: Unger fullname: Unger, Robert H organization: Harvard T.H. Chan School of Public Health, Boston, Massachusetts – sequence: 10 givenname: Alex M surname: Tinianow fullname: Tinianow, Alex M organization: Harvard T.H. Chan School of Public Health, Boston, Massachusetts – sequence: 11 givenname: Swen-Olof surname: Andersson fullname: Andersson, Swen-Olof organization: School of Health and Medical Sciences, Örebro University, Örebro, Sweden – sequence: 12 givenname: Ove surname: Andrén fullname: Andrén, Ove organization: School of Health and Medical Sciences, Örebro University, Örebro, Sweden – sequence: 13 givenname: Katja surname: Fall fullname: Fall, Katja organization: School of Health and Medical Sciences, Örebro University, Örebro, Sweden – sequence: 14 givenname: Michelangelo surname: Fiorentino fullname: Fiorentino, Michelangelo organization: Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Bologna, Italy – sequence: 15 givenname: Lorelei A surname: Mucci fullname: Mucci, Lorelei A email: lmucci@hsph.harvard.edu organization: Division of Public Health Sciences, University of Iceland, Reykjavik, Iceland
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Snippet	Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that the presence of... Background: Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that the...
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SubjectTerms	Adult Aged Cohort Studies Humans Male Middle Aged Neoplasm Grading - methods Neoplasm Invasiveness - pathology Peripheral Nerves - pathology Prostatic Neoplasms - pathology
Title	Perineural Invasion and Risk of Lethal Prostate Cancer
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