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.