Topographic and quantitative relationship between prostate inflammation, proliferative inflammatory atrophy and low-grade prostate intraepithelial neoplasia: A biopsy study in chronic prostatitis patients

Abstract

Inflammatory processes are important components in the pathogenesis of many human cancers. According to the ‘injury and regeneration’ model for prostate carcinogenesis, injury caused by pathogens or pro-inflammatory cytotoxic agents would trigger proliferation of prostatic glandular cells, leading to the appearance of epithelial lesions named ‘Proliferative Inflammatory Atrophy’ (PIA). Inflammatory cells infiltrating the prostate would release genotoxic reactive oxygen species, leading atrophic cells to neoplastic progression. The hypothesis pointing to PIA as risk-lesion for prostate cancer has been extensively investigated at the cellular and molecular levels, but few morphological data are available linking PIA or prostatic intraepithelial neoplasia (PIN) to inflammation or clinical prostatitis. We investigated at the morphological level 1367 prostate biopsies from 98 patients with a recent history of chronic prostatitis, and 32 patients with biopsies positive for carcinoma. Our results show that i) PIA is found more frequently in biopsy cores containing a severe or moderate inflammatory focus, compared to NON-PIA lesions (partial or cystic atrophy); ii) the PIA lesion post-atrophic hyperplasia is more frequently found in tissues showing mild or no inflammation; iii) the extent of PIA per patient correlates with the burden of moderate or severe inflammation, whereas NON-PIA lesions do not; iv) low-grade PIN is in over 90% of cases emerging from normal, non-atrophic glands and is more frequently found in biopsy cores with absent or mild inflammatory burden; v) the inverse relationship between the prevalence of low-grade PIN and the extent of PIA lesions per patient is described by a power law function, suggesting the low likelihood of the concomitant presence of these lesions in the same tissue; vi) NON-PIA lesions correlate inversely with neoplasia in patients with prostate cancer; vii) the total scores of the NIH-CPSI questionnaire correlate with both PIA and inflammation burdens at diagnosis of prostatitis but not after pharmacological intervention. These results point to a positive association between tissue inflammation, clinical prostatitis and the putative cancer risk-lesion PIA, but do not support a model whereby low-grade PIN would arise from PIA.

Influence of chronic inflammation on Bcl-2 and PCNA expression in prostate needle biopsy specimens

“…This suggestion is based on the following findings: i) Morphological overlap between PIA and HGPIN; ii) the phenotypes of many of the cells in PIA are most consistent with that of immature secretory-type cells, similar to that of the cells of HGPIN; and iii) PIA, HGPIN and carcinoma all occur with high prevalence in the peripheral zone and low prevalence in the central zone of the prostate. In the present study on needle-biopsy specimens, a close topographic association between PIA/PAH and HGPIN was observed, in agreement with the findings in previous studies (18,21). …”

“…This shift is present in most of the carcinoma precursor lesions, including HGPIN. It has long been hypothesized that PIA may be a precursor of prostate cancer, as several studies have reported a morphological transition from PIA to HGPIN (18,21). This suggestion is based on the following findings: i) Morphological overlap between PIA and HGPIN; ii) the phenotypes of many of the cells in PIA are most consistent with that of immature secretory-type cells, similar to that of the cells of HGPIN; and iii) PIA, HGPIN and carcinoma all occur with high prevalence in the peripheral zone and low prevalence in the central zone of the prostate.…”

“…It has been hypothesized that the atrophic epithelial cells in PIA lesions are the targets of neoplastic transformation and potentially give rise to carcinoma. PAH has been shown to be closely associated with persistent chronic inflammation (21). PAH represents ‘post-inflammatory’ atrophic lesions.…”

“…PAH is occasionally confused with carcinoma due to its overlapping architectural and nuclear features. In particular, these lesions are predominantly composed of small crowded glands, usually surrounded by centrally situated and dilated large ducts, irregular and atrophic-appearing contours lined by flattened-to-cuboidal epithelial cells, with nuclear enlargement and prominent nucleoli (21,22). PIA/PAH lesions have been reported to show increased proliferative activity compared with benign prostatic epithelium and simple atrophy (SA) (23).…”

Histopathologic Characterization of Prostate Diseases in Madinah, Saudi Arabia

“…Although BPH is predominantly attributed to aging, genetic factors and hormonal disturbances (Nicholson and Ricke, 2011), a possible role of obesity, diet and life style is also under investigation (Tewari et al, 2012;Goluch-Koniuszy et al, 2013). Similarly the significance of chronic inflammation in pathogenesis of BPH has recently emerged (Fibbi et al, 2010) and emphasized by recent publications (Vral et al, 2012;Bostanci et al, 2013;of cancer death (Brawley, 2012a). Screening programs have increased risk of diagnosis among younger men in their 40s and 50s (Brawley, 2012b).…”