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.

BK Virus as a Cofactor in the Etiology of Prostate Cancer in Its Early Stages

“…Epithelial cells in PIA are highly proliferative, exhibit phenotypic characteristics intermediate between those of secretory and basal cells, and have been proposed to be precursors of prostatic neoplastic transformation (89). Merging of focal areas of PIA with PIN has also been reported (18). Interestingly, the occurrence of mutations in p53 or Rb1 in PIA is low, supporting a viral cause for the transition of benign epithelium to PIA lesions through the inactivation of these tumor suppressors by viral oncoproteins.…”

Inflammation in prostate carcinogenesis

“…The morphological manifestation of this injury is focal atrophy or PIA, which we postulate to be a signature of the 'field effect' of prostate carcinogenesis. The biological manifestations are an increase in proliferation and a massive increase in epithelial cells that possess a phenotype intermediate between basal cells and mature luminal cells 5,6,23 . In a small subset of cells, perhaps cells with an intermediate phenotype that contain at least some 'stem cell' properties, somatic genome alterations occur, such as cytosine methylation within the CpG island of the GSTP1 gene and telomere shortening.…”

“…The objective of this Review is to take a multidisciplinary approach to present and analyse such studies. Because several reviews related to these topics have been published [5][6][7] , here we will focus on new findings and ideas with the purpose of sparking innovative areas of investigation that might ultimately lead to the prevention of prostate cancer. …”

Tumor-associated Antigen Arrays for the Serological Diagnosis of Cancer

“…There is growing evidence that an augmented state of cellular oxidative stress (ASCOS), associated with a proinflammatory environment, plays a major role in prostate carcinogenesis (68,69). This evidence is derived (68,69).…”