Date Published: January 12, 2017
Publisher: Public Library of Science
Author(s): Tomoya Kakegawa, Yuan Bae, Takashi Ito, Keisuke Uchida, Masaki Sekine, Yutaka Nakajima, Asuka Furukawa, Yoshimi Suzuki, Jiro Kumagai, Takumi Akashi, Yoshinobu Eishi, Andrew McDowell.
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.
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).
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. 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.
Cancer in several organs, including the stomach, liver, and large intestine, has been linked to chronic infection and inflammation. Evidence from epidemiologic, histopathologic, and molecular pathologic studies indicates that chronic inflammation also contributes to prostate cancer [1,2]. Propionibacterium acnes is a commensal bacteria that is frequently detected in prostate tissue with prostatitis and prostate cancer (PCa) [3–6]. P. acnes infection changes cell proliferation, and enables epithelial cells to grow in an anchorage-independent manner, which can lead to cellular transformation . Thus, P. acnes infection is likely involved in the initiation and/or progression of PCa.
The frequency of P. acnes-positive glands was higher in samples from PCa patients than control patients in the prostate core needle biopsy samples, as previously found in radical prostatectomy specimens. The increased frequency of P. acnes-positive glands in patients with PCa suggests not only that this indigenous bacterium contributes to prostate carcinogenesis but also that the frequency can be used in the risk assessment for patients after the first negative prostate biopsy performed due to an increased PSA titer. According to the results obtained in the present study with limited numbers of PCa and control patients who underwent repeated biopsy in our university hospital, the risk that the first biopsy was a false negative was 14 times higher in patients with than in those without an increased frequency of P. acnes-positive glands in their biopsy samples, and the risk assessment power with the first negative biopsy samples was superior to the serum PSA titer of patients at the time of the first biopsy.