title: Pathological and molecular mechanisms of prostate carcinogenesis: implications for diagnosis, detection, prevention, and treatment.
abstract: Prostate cancer is an increasing threat throughout the world. As a result of a demographic shift in population, the number of men at risk for developing prostate cancer is growing rapidly. For 2002, an estimated 189,000 prostate cancer cases were diagnosed in the U.S., accompanied by an estimated 30,200 prostate cancer deaths [Jemal et al., 2002]. Most prostate cancer is now diagnosed in men who were biopsied as a result of an elevated serum PSA (>4 ng/ml) level detected following routine screening. Autopsy studies [Breslow et al., 1977; Yatani et al., 1982; Sakr et al., 1993], and the recent results of the Prostate Cancer Prevention Trial (PCPT) [Thompson et al., 2003], a large scale clinical trial where all men entered the trial without an elevated PSA (<3 ng/ml) were subsequently biopsied, indicate the prevalence of histologic prostate cancer is much higher than anticipated by PSA screening. Environmental factors, such as diet and lifestyle, have long been recognized contributors to the development of prostate cancer. Recent studies of the molecular alterations in prostate cancer cells have begun to provide clues as to how prostate cancer may arise and progress. For example, while inflammation in the prostate has been suggested previously as a contributor to prostate cancer development [Gardner and Bennett, 1992; Platz, 1998; De Marzo et al., 1999; Nelson et al., 2003], research regarding the genetic and pathological aspects of prostate inflammation has only recently begun to receive attention. Here, we review the subject of inflammation and prostate cancer as part of a "chronic epithelial injury" hypothesis of prostate carcinogenesis, and the somatic genome and phenotypic changes characteristic of prostate cancer cells. We also present the implications of these changes for prostate cancer diagnosis, detection, prevention, and treatment.
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21231-1000, USA. ademarz@jhmi.edu
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.forename: Theodore L
authors.initials: TL
authors.lastname: DeWeese
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.forename: Alan K
authors.initials: AK
authors.lastname: Meeker
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: William G
authors.initials: WG
authors.lastname: Nelson
mesh_terms: D001284:Atrophy / Q000503:physiopathology; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D051059:PTEN Phosphohydrolase; D010750:Phosphoproteins / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D011506:Proteins / Q000235:genetics; D019998:Racemases and Epimerases / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D015398:Signal Transduction; D016615:Telomere / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; D010750:Phosphoproteins; D011506:Proteins; D011944:Receptors, Androgen; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D012697:Serine Endopeptidases; C055645:hepsin; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase