Focal prostate atrophy has several recognizable morphological patterns. It is rapidly becoming of great interest to many investigators. Although its etiology remains unknown, its relation to inflammation, PIN, BPH, and carcinoma is being explored by a number of new molecular approaches, as well as by traditional pathological association studies. Prostate inflammation also has several morphological patterns and is exceedingly common. Except in relatively rare cases in which infection can be demonstrated, prostate inflammation is also of largely unknown etiology. Animal studies have implicated dietary factors, such as lack of soy, and neonatal estrogen exposure, as potential factors that trigger an autoimmune response (99-101).
A model has been proposed (3,4) that suggests that repeated bouts of injury to the prostate epithelium, presumably as a result of inflammation in response to unknown pathogens or autoimmune disease and/or dietary factors, result in proliferation of epithelial cells that possess a phenotype intermediate between basal cells and mature luminal cells. These cells are hypothesized to be attempting tissue repair. This is supported by the finding that several proteins known to be involved in tissue repair, such as C-met (25) and hepatocyte activator inhibitor-1 (74), show elevated expression in focal atrophy. The model predicts that in a small subset of cells somatic genome alterations occur, such as such as cytosine hypermethylation within the CpG island of the GSTP1 gene and telomere shortening, that drive genetic instability and initiate high-grade PIN and prostate cancer formation. A classification system of focal atrophy lesions (17) was recently validated that should aid in further testing this model by various groups in human patho-epidemiological and ecological studies. In addition, an improved understanding of the molecular pathogenesis of prostate atrophy and inflammation and new animal models of prostate inflammation are needed to further test this model vigorously in experimental settings.
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