Mismatch repair proteins in recurrent prostate cancer.

Normal cell function requires strict control over the repair of DNA damage, which prevents excessive mutagenesis. An enhanced accumulation of mutations results in the multistep process generally known as carcinogenesis. Defects in repair pathways fuel such mutagenesis by allowing reiterative cycles of mutation, selection, and clonal expansion that drive cancer progression. The repair of mismatches is an important mechanism in the prevention of such genetic instability. In addition, proteins of this pathway have the unique ability to function in DNA damage response by inducing apoptosis when irreparable damage is encountered. Though originally identified primarily in association with a predisposition to hereditary colon cancer, mismatch repair defects have been identified in many other cancer types, including prostate cancer. From the first discovery of microsatellite instability in prostate cancer cell lines and tumor samples, variations in protein levels and a possible association with recurrence and aggression of disease have been described. Current results suggest that the involvement of mismatch repair proteins in prostate cancer may differ from that found in colorectal cancer, in the type of proteins and protein defects involved and the type of causative mutations. Additional work is clearly needed to investigate this involvement and the possibility that such defects may affect treatment response and androgen independence.