title: Frequency of Propionibacterium acnes Infection in Prostate Glands with Negative Biopsy Results Is an Independent Risk Factor for Prostate Cancer in Patients with Increased Serum PSA Titers.
abstract: BACKGROUND
  Propionibacterium acnes has recently been implicated as a cause of chronic prostatitis and this commensal bacterium may be linked to prostate carcinogenesis. The occurrence of intracellular P. acnes infection in prostate glands and the higher frequency of P. acnes-positive glands in radical prostatectomy specimens from patients with prostate cancer (PCa) than in those from patients without PCa led us to examine whether the P. acnes-positive gland frequency can be used to assess the risk for PCa in patients whose first prostate biopsy, performed due to an increased prostate-specific antigen (PSA) titer, was negative.
  
  
  METHODS
  We retrospectively collected the first and last prostate biopsy samples from 44 patients that were diagnosed PCa within 4 years after the first negative biopsy and from 36 control patients with no PCa found in repeated biopsy for at least 3 years after the first biopsy. We evaluated P. acnes-positive gland frequency and P. acnes-positive macrophage number using enzyme-immunohistochemistry with a P. acnes-specific monoclonal antibody (PAL antibody).
  
  
  RESULTS
  The frequency of P. acnes-positive glands was higher in PCa samples than in control samples in both first biopsy samples and in combined first and last biopsy samples (P < 0.001). A frequency greater than the threshold (18.5 and 17.7, respectively) obtained by each receiver operating characteristic curve was an independent risk factor for PCa (P = 0.003 and 0.001, respectively) with odds ratios (14.8 and 13.9, respectively) higher than those of serum PSA titers of patients just before each biopsy (4.6 and 2.3, respectively). The number of P. acnes-positive macrophages did not differ significantly between PCa and control samples.
  
  
  CONCLUSIONS
  These results suggested that the frequency of P. acnes-positive glands in the first negative prostate biopsy performed due to increased PSA titers can be supportive information for urologists in planning repeated biopsy or follow-up strategies.
authors.affiliation: Department of Human Pathology, Graduate School and Faculty of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kakegawa
authors.affiliation: Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, Tokyo, Japan.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Bae
authors.affiliation: Department of Human Pathology, Graduate School and Faculty of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Sekine
authors.affiliation: Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakajima
authors.affiliation: Department of Human Pathology, Graduate School and Faculty of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Furukawa
authors.affiliation: Department of Human Pathology, Graduate School and Faculty of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Pathology, Yokohama City Minato Red Cross Hospital, Yokohama, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Kumagai
authors.affiliation: Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, Tokyo, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Akashi
authors.affiliation: Department of Human Pathology, Graduate School and Faculty of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.|Division of Surgical Pathology, Tokyo Medical and Dental University Hospital, Tokyo, Japan.
authors.forename: Yoshinobu
authors.identifier: http://orcid.org/0000-0002-0521-1670
authors.initials: Y
authors.lastname: Eishi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D019540:Area Under Curve; D016022:Case-Control Studies; D016908:Gram-Positive Bacterial Infections / Q000175:diagnosis*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011425:Propionibacterium acnes / Q000502:physiology*; D011467:Prostate / Q000382:microbiology* / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000382:microbiology*; D011472:Prostatitis / Q000382:microbiology / Q000473:pathology; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D000911:Antibodies, Monoclonal; D017430:Prostate-Specific Antigen