Frequency of <i>Propionibacterium acnes</i> Infection in Prostate Glands with Negative Biopsy Results Is an Independent Risk Factor for Prostate Cancer in Patients with Increased Serum PSA Titers

<div><p>Background</p><p><i>Propionibacterium acnes</i> has recently been implicated as a cause of chronic prostatitis and this commensal bacterium may be linked to prostate carcinogenesis. The occurrence of intracellular <i>P</i>. <i>acnes</i> infection in prostate glands and the higher frequency of <i>P</i>. <i>acnes</i>-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 <i>P</i>. <i>acnes</i>-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.</p><p>Methods</p><p>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 <i>P</i>. <i>acnes</i>-positive gland frequency and <i>P</i>. <i>acnes</i>-positive macrophage number using enzyme-immunohistochemistry with a <i>P</i>. <i>acnes</i>-specific monoclonal antibody (PAL antibody).</p><p>Results</p><p>The frequency of <i>P</i>. <i>acnes</i>-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 <i>P</i>. <i>acnes</i>-positive macrophages did not differ significantly between PCa and control samples.</p><p>Conclusions</p><p>These results suggested that the frequency of <i>P</i>. <i>acnes</i>-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.</p></div

<i>P</i>. <i>acnes</i>-positive glands and <i>P</i>. <i>acnes</i>-positive macrophages in the negative prostatic needle biopsy samples detected by IHC with PAL antibody.

<p>Two representative areas with many <i>P</i>. <i>acnes</i>-positive glands or <i>P</i>. <i>acnes</i>-positive macrophages are shown pairwise (A-B or C-D, respectively) with hematoxylin and eosin staining (A, C) and IHC with the PAL antibody (B, D). A-B: Many <i>P</i>. <i>acnes</i>-positive glands are clustered in an area of the first negative biopsy sample from a patient with PCa. The antibody reacted with a few small round bodies in some epithelial cells, as shown in the inset, of the gland indicated by an arrow. C-D: <i>P</i>. <i>acnes</i>-positive macrophages are clustered in some areas of stromal inflammatory cell infiltration of the first negative biopsy samples from a patient with PCa. The antibody reacted with many small round bodies, as shown in the inset, of the macrophages indicated by an arrow.</p

Mean score of <i>P</i>. <i>acnes</i>-positive glands.

<p>PCa: samples from PCa patients, Control: samples from control patients, First: first biopsy samples, Last: last biopsy samples, Total: first and last biopsy samples combined, NS: not significant.</p

Clinicopathologic profiles of the patients.

<p>Clinicopathologic profiles of the patients.</p

Time line diagram for the biopsy sampling.

<p>PCa(-) means negative biopsy where no cancer lesion was found in any cores of the biopsy sample. PCa(+) means positive biopsy where cancer lesion was found in one or more cores of the biopsy sample. Interval between the first and last biopsy varied from 1 month to 4 years in the PCa patients and from 3 years to 11 years in the control patients.</p

Receiver operating characteristic curves for the mean score of <i>P</i>. <i>acnes</i>-positive glands.

<p>A) Analysis of the results from first biopsy samples with and without PCa. B) Analysis of the results from both the first and last biopsy samples with and without PCa.</p

Frequency of <i>P</i>. <i>acnes</i>-positive glands, number of <i>P</i>. <i>acnes</i>-positive macrophages, serum PSA titers, and grade of chronic inflammation.

<p>A) Frequency (%) of <i>P</i>. <i>acnes</i>-positive glands. B) Number of <i>P</i>. <i>acnes</i>-positive macrophage. C) Serum PSA titer. D) Grade of chronic inflammation. PCa: samples from PCa patients, Control: samples from control patients, First: first biopsy samples, Last: last biopsy samples, Total: first and last biopsy samples combined, NS: not significant.</p

Logistic regression analysis with the frequency of <i>P</i>. <i>acnes</i>-positive glands.

<p>Logistic regression analysis with the frequency of <i>P</i>. <i>acnes</i>-positive glands.</p

Receiver operating characteristic curves for the frequency of <i>P</i>. <i>acnes</i>-positive glands and serum PSA titer.

<p>A) Analysis of the results from first biopsy samples with and without PCa. B) Analysis of the results from both the first and last biopsy samples with and without PCa. <i>P</i>. <i>acnes</i> IHC: the frequency of <i>P</i>. <i>acnes</i>-positive glands, PSA: serum PSA titer</p

Logistic regression analysis with the mean score of <i>P</i>. <i>acnes</i>-positive glands.

<p>Logistic regression analysis with the mean score of <i>P</i>. <i>acnes</i>-positive glands.</p