UROLOGICAL SURVEY   ( Download pdf )

 

PATHOLOGY

Propionibacterium acnes associated with inflammation in radical prostatectomy specimens: a possible link to cancer evolution?
Cohen RJ, Shannon BA, McNeal JE, Shannon T, Garrett KL
Uropath Pty Ltd, Perth, Western Australia
J Urol. 2005; 173: 1969-74

  • Purpose: Inflammation is commonly observed in the prostate gland and has been implicated in the development of prostate cancer. The etiology of prostatic inflammation is unknown. However, the involvement of a carcinogenic infectious agent has been suggested.
  • Materials and Methods: Prostatic tissue from 34 consecutive patients with prostate cancer was cultured to detect the presence of bacterial agents. Prostatic inflammation was assessed by histological examination of wholemount tissue sections.
  • Results: The predominant microorganism detected was Propionibacterium acnes, found in 35% of prostate samples. A significantly higher degree of prostatic inflammation was observed in cases culture positive for P. acnes (p = 0.007). P. acnes was separated into 3 groups based on cell surface properties, phenotype and genetic grouping. All skin control isolates were classified as group 1 whereas most prostatic isolates were classified as groups 2 and 3.
  • Conclusions: P. acnes has been isolated from prostatic tissues in men who underwent radical prostatectomy for localized cancer and has been shown to be positively associated with prostatic inflammation. This inflammation may then be linked to the evolution of carcinoma. Furthermore, organisms infecting these patients with prostate cancer differ genetically and phenotypically from the commonly identified cutaneous P. acnes isolates, suggesting that specific subtypes may be involved in development of prostatic inflammation.

  • Editorial Comment
    This is a very exciting article considering that recently the authors that implicated Helicobacter pylori to the pathogenesis of both peptic ulcer and gastric carcinoma were awarded the Nobel Prize.
    Chronic inflammation of longstanding duration has been linked to the development of carcinoma in several organ systems (1-3). In the prostate, chronic inflammation is associated with both postatrophic hyperplasia and focal simple atrophy (4). De Marzo et al. (5) propose combining these lesions into a category called proliferative inflammatory atrophy (PIA). The authors suggest that PIA may be a precursor to prostatic adenocarcinoma. They also suggest that there are morphological transitions within the same acinar/duct unit, between high-grade prostatic intraepithelial neoplasia (HGPIN) and PIA that occur frequently (5). This finding supports a model whereby the proliferative epithelium in PIA may progress to HGPIN.
    This hypothesis is challenged by others. Anton et al. (6) studying radical prostatectomies concluded that postatrophic hyperplasia is a relatively common lesion present in about one-third of prostates, either with or without prostate carcinoma. The authors found no association between the presence of prostatrophic hyperplasia and the likelihood of cancer and no topographic association between postatrophic hyperplasia and prostate carcinoma foci. This held for both clinical cancer in a radical prostatectomy specimen and incidental cancer in a cystoprostatectomy specimen (6). Bakshi et al. (7) studied 79 consecutive prostate biopsies. 54% of initial biopsies were benign, 42% of the cases showed cancer, and 4% HGPIN or atypia. Postatrophic hyperplasia was seen in 17% of benign initial biopsies with available follow-up. Of these, 75% had associated inflammation. There was no significant difference in the subsequent diagnosis of prostate cancer for groups with postatrophic hyperplasia, partial atrophy, atrophy, or no specific abnormality. The authors conclude that the subcategories of atrophy do not appear to be associated with a significant increase in the risk of diagnosis of prostate cancer subsequently. Billis & Magna (8) studied 100 consecutive autopsies of men older than 40 years. Prostatic atrophy without (group A) and with inflammation (group B) was correlated with age, race, histologic (incidental) carcinoma, HGPIN, and extent of both these lesions. No statistically significant difference was found between the groups. Furthermore, neither a topographical relation nor a morphologic transition was seen between prostatic atrophy and histologic carcinoma or HGPIN. In a recent paper, Postma et al. (9) evaluated whether the incidence of atrophy on sextant biopsies is associated with subsequent prostate cancer detection and did not find a greater prostate cancer or HGPIN incidence during subsequent screening rounds.
    The authors of the article surveyed found a positive association between P. acnes and prostatic inflammation, which may be implicated in the development of prostate cancer. However, they comment that it is possible that prostatic inflammation will also be caused by other microorganisms which could not be identified by the study, for example obligate anaerobes or species which are difficult to culture under laboratory conditions. They also comment on a second important limitation of the study related to the lack of appropriate negative controls such as prostate tissue from patients without inflammation, atrophy and cancer.

References
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4. Putzi MJ, De Marzo AM: Morphological transitions between proliferative inflammatory atrophy and high-grade prostatic intraepithelial neoplasia. Urology. 2000; 56: 828-832.
5. De Marzo AM, Marchi VL, Epstein JI, Nelson WG: Proliferative inflammatory atrophy of the prostate. Implications for prostatic carcinogenesis. Am J Pathol. 1999; 155: 1985-1992.
6. Anton RC, Kattan MW, Chakraborty S, Wheeler TM: Postatrophic hyperplasia of the prostate. Lack of association with prostate cancer. Am J Surg Pathol. 1999; 23: 932-936.
7. Bakshi NA, Pandya S, Schervish EW, Wojno KJ: Morphologic features and clinical significance of post-atrophic hyperplasia in biopsy specimens of prostate. Mod Pathol (abst). 2002; 15: 154A.
8. Billis A, Magna LA: Inflammatory atrophy of the prostate. Prevalence and significance. Arch Pathol Lab Med. 2003; 127: 840-4.
9. Postma R, Schröder FH, van der Kwast TH: Atrophy in prostate needle biopsy cores and its relationship to prostate cancer incidence in screened men. Urology. 2005; 65: 745-9.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil