Acute inflammatory proteins constitute the organic matrix of prostatic corpora amylacea and calculi in men with prostate cancer

Abstract

Corpora amylacea (CA) are a frequent microscopic finding in radical prostatectomy specimens from men undergoing treatment for prostate cancer. Although often observed histologically to be associated with inflammation, the contribution of CA to prostatitis-related symptoms of unknown etiology or to prostate carcinogenesis remains unclear. Prostatic calculi (PC), which potentially represent calcified forms of CA, are less common but can cause urological disease including urinary retention and prostatitis. We conducted a comprehensive compositional analysis of CA/PC to gain insight into their biogenesis. Infrared spectroscopy analysis of calculi collected from 23 patients confirmed a prevalence of calcium phosphate in the form of hydroxyapatite. This result sets PC apart from most urinary stones, which largely are composed of calcium oxalate. Tandem mass spectrometry-based proteomic analysis of CA/PC revealed that lactoferrin is the predominant protein component, a result that was confirmed by Western blot analysis. Other proteins identified, including calprotectin, myeloperoxidase, and ␣-defensins, are proteins contained in neutrophil granules. Immunohistochemistry (IHC) suggested the source of lactoferrin to be prostate-infiltrating neutrophils as well as inflamed prostate epithelium; however, IHC for calprotectin suggested prostate-infiltrating neutrophils as a major source of the protein, because it was absent from other prostate compartments. This study represents a definitive analysis of the protein composition of prostatic CA and calculi and suggests that acute inflammation has a role in their biogenesis-an intriguing finding, given the prevalence of CA in prostatectomy specimens and the hypothesized role for inflammation in prostate carcinogenesis.acute inflammation ͉ lactoferrin ͉ neutrophil ͉ hydroxyapatite ͉ prostatic calculi

Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit

“…3). CA stained very strongly for lactoferrin, showing an unstained ring structure, as expected (Sfanos et al 2009). Prostate from control and HFDC testosterone showed scanty positivity for lactoferrin (Fig.…”

“…Corpora amylacea are protein aggregates of lactoferrin (Sfanos et al 2009), delivered by neutrophils following acute prostate inflammation (Legrand et al 2005, Sfanos et al 2009). As expected (De Marzo et al 2007, Sfanos et al 2009, Yanamandra et al 2009), we have observed corpora amylacea adjacent to infiltrating inflammatory cells. Gene expression of macrophage, neutrophil, and CD4…”

Are prostatic calculi independent predictive factors of lower urinary tract symptoms?

“…Prostatic calculi are presumed to form by the precipitation of prostatic secretions and calcification o f t h e c o r p o r a a m y l a c e a u n d e r i n f l a m m a t o r y conditions [1,2]. The precise mechanisms by which calculi form and the association of calculi with benign and malignant conditions of the prostate gland are unknown.…”

Clinical and Biochemical Influence of Prostatic Stones

“…This discrepancy may be due in part to new and more appropriate methods available nowadays that allow the detection of chronic inflammation and infection with greater precision. Recently published studies showed that acute phase proteins predominated in the structure of prostatic stones [25,26] . In addition, bacterial biofilm was found in the prostatic stones and high frequency of bacterial imprints was found in these stones by electron microscopy scanning [27][28][29] .…”