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Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to risk of lethal prostate cancer
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Mol Pathol Lab, Addarii Inst Oncol, Dept Hematol Oncol, Univ Bologna, Bologna, Italy; Sch Med, Dana Farber Canc Inst, Dept Pathol, Brigham & Womens Hosp & Adult Oncol, Harvard Univ, Boston MA, USA.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Sch Med, Channing Lab, Dept Med, Brigham & Womens Hosp, Harvard Univ, Boston MA, USA; Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
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2011 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 10, p. 2280-2287Article in journal (Refereed) Published
Abstract [en]

Background: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. Methods: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression. Results: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42). Conclusion: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. Impact: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease. Cancer Epidemiol Biomarkers Prev; 20(10); 2280-7. (C) 2011 AACR.

Place, publisher, year, edition, pages
2011. Vol. 20, no 10, p. 2280-2287
National Category
Urology and Nephrology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-30105DOI: 10.1158/1055-9965.EPI-11-0373ISI: 000295717900034OAI: oai:DiVA.org:oru-30105DiVA, id: diva2:638754
Available from: 2013-08-02 Created: 2013-08-02 Last updated: 2018-05-05Bibliographically approved
In thesis
1. Infection induced chronic inflammation and it's association with prostate cancer initiation and progression
Open this publication in new window or tab >>Infection induced chronic inflammation and it's association with prostate cancer initiation and progression
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

An association between cancer development and inflammation has long been suggested. Approximately 20% of all human cancers in adults are assumed to result from chronic inflammation. The aim of this thesis was to investigate if infection-induced chronic inflammation plays a role in prostate carcinogenesis.

Our results revealed a greater infiltration of the bacterium Propionibacterium acnes in the prostate tissue obtained from men with prostate cancer compared to men without any histological evidence of the disease. These findings indicate that prostate cancer could potentially be included in the list of cancers with an infectious etiology.

Further, we investigated whether chronic inflammation has a role in disease progression. Our results demonstrated that men with lethal prostate cancer had pronounced infiltration of immune cells with suppressive function of the anti-tumor immune response compared to men with a more indolent prostate cancer.

Confirmation of our results may open up avenues for targeted prostate cancer treatment by offering men with chronic inflammation alternative therapies such as anti-inflammatory drugs. If the involvement of P. acnes in prostate cancer development is replicated in other studies, vaccination therapies may be feasible. To further individualize prostate cancer therapy, bolstering the anti-tumor immune response in order to reduce tumor progression may be determined to be advantageous for some patients.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013. p. 65
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 86
Keyword
Prostate cancer, chronic inflammation, CD4 helper T cells, CD8 cytotoxic T cells, regulatory T cells, Propionibacterium acnes
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-28466 (URN)978-91-7668-920-2 (ISBN)
Public defence
2013-05-31, Wilandersalen, Universitetssjukhuset i Örebro, Södra Grev Rosengatan 18, 703 62 Örebro, 09:00 (Swedish)
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Supervisors
Available from: 2013-03-25 Created: 2013-03-25 Last updated: 2017-10-17Bibliographically approved

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Davidsson, SabinaAndrén, OveFall, Katja
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