Abstract
BackgroundPropionibacterium 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.MethodsWe 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).ResultsThe 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.ConclusionsThese 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.
Highlights
Cancer in several organs, including the stomach, liver, and large intestine, has been linked to chronic infection and inflammation
The number of P. acnes-positive macrophages did not differ significantly between prostate cancer (PCa) and control samples. These results suggested that the frequency of P. acnes-positive glands in the first negative prostate biopsy performed due to increased prostate-specific antigen (PSA) titers can be supportive information for urologists in planning repeated biopsy or follow-up strategies
The morphology of the bodies detected with the PAL antibody was similar to that of cultured epithelial cells infected with P. acnes in vitro at 5 days postinfection and that of prostate glandular epithelial cells in mice infected by transurethral injection of P. acnes in vivo at 1 or 2 weeks postinfection (S3 and S4 Figs)
Summary
Cancer in several organs, including the stomach, liver, and large intestine, has been linked to chronic infection and inflammation. We recently created an anti-P. acnes monoclonal antibody (PAL antibody) that recognizes an epitope of the lipoteichoic acid that is shared by all strains of phylotype I P. acnes [7] This PAL antibody could be used in enzyme immunohistochemistry (IHC) to detect P. acnes within non-cancerous glandular epithelium and stromal macrophages in formalin-fixed paraffinembedded (FFPE) prostate samples [7]. Double labeling of cytoplasmic P. acnes and nuclear NFkB expression in prostate tissue sections revealed that NF-kB expression is more frequent in P. acnes-infected glands than in glands without P. acnes infection [7] These results suggested that latent intraepithelial P. acnes infection in non-cancerous prostate glands contributes to carcinogenesis in the prostate. 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
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