Prostate Cancer Linked to High Levels of a Mismatch Repair Protein

Alixanna M. Norris
Wake Forest University School of Medicine
T32ES007331

A Ph.D. candidate at the Wake Forest School of Medicine supported by NIEHS identified an increase in a DNA mismatch repair protein as a marker for prostate cancer. This finding represents the first documented evidence of an increase in a mismatch repair protein being associated with human cancer.

The purpose of the study was to identify new prognostic tools to identify prostate cancer patients at risk for particularly severe life-threatening forms of the disease compared to those that develop slower growing less severe forms. The research team analyzed tissue samples from prostatectomies and determined the presence or absence of the key mismatch repair proteins MSH2, MLH1, and PMS2. They found increases in PMS2 in the samples from prostate cancer tissue. Many previous studies have associated deficits in mismatch repair proteins with risks for tumor formation. The results also demonstrate that the PMS2 increase is associated with genetic instability.

The study results imply that the increase in PMS2 and the accompanying genetic instability are early events in the development of prostate cancer. The results also suggest that PMS2 may be used as a prognostic marker for the early detection of aggressive forms of prostate cancer and could be used to direct individual treatment strategies for patients with the marker.

Citation: Norris AM, Woodruff RD, D'Agostino RB Jr, Clodfelter JE, Scarpinato KD. Elevated levels of the mismatch repair protein PMS2 are associated with prostate cancer. Prostate. 2007 Feb 1;67(2):214-25.