Chronic bacterial inflammation induces prostatic intraepithelial neoplasia in mouse prostate.
BACKGROUND
Although the aetiology of prostate cancer remains unknown, we hypothesised that chronic bacterial insult has a major role in prostate carcinogenesis.


METHODS
Male C3H/HeOuJ mice, infected with phosphate-buffered saline or Escherichia coli bacteria, were killed at 5 days, or at 12 or 26 weeks. Harvested prostate tissues were evaluated for inflammatory responses and immunostained for neoplastic transformation markers.


RESULTS
All infected mice developed bacterial prostatitis. Control mice had no prostate infections or inflammation. Mice infected for 5 days showed foci of acute inflammation with infiltrating neutrophils and epithelial necrotic debris in the prostatic glandular lumen. All mice infected for 12 weeks had evidence of chronic inflammation with dense inflammatory infiltrates in the stroma. The prostatic epithelium showed varying degrees of atypical hyperplasia with increased epithelial cell layers and cytological atypia. At 26 weeks, the dysplastic changes were more pronounced and mimicked a prostatic intraepithelial neoplasia and high-grade dysplasia. Prostatic glands exhibiting reactive dysplasia had a stronger staining for oxidative DNA damage, increased epithelial cell proliferation, and a decrease in androgen receptor, GSTP1, p27(Kip1), and PTEN expression, when compared with control prostate glands.


CONCLUSIONS
These data demonstrate that chronic inflammation induces focal prostatic glandular atypia and suggest a potential linkage between inflammation and prostatic neoplasia.
Department of Internal Medicine, Section of Adult Oncology and Hematology and GU Oncology Research Laboratory, University of Nebraska Medical Center, Omaha, NE 68198-7680, USA. jelkahwaji@unmc.edu
J E
JE
Elkahwaji
R J
RJ
Hauke
C M
CM
Brawner
D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology; D004927:Escherichia coli Infections / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D019048:Prostatic Intraepithelial Neoplasia / Q000382:microbiology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D011472:Prostatitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*