The elevated expression of a mismatch repair protein is a predictor for biochemical recurrence after radical prostatectomy.
OBJECTIVE
The inability to predict clinical outcome of prostate cancer is a major impediment to effective treatment decisions and patient counseling. New markers of recurrence are needed to improve the accuracy of risk assessment and treatment of prostate cancer. Our previous studies identified a mismatch repair protein, PMS2, to be elevated in prostate cancer; here, we investigate the prognostic potential of this marker. We hypothesized that the elevation of PMS2 would correlate with disease outcome.


METHODS
Retrospective quantitative immunohistochemistry was done to measure PMS2 in high-grade cancers of 166 men treated by radical prostatectomy with a biochemical recurrence rate of 56%. Associations between PMS2 levels, pathologic variables, and biochemical recurrence over time were determined.


RESULTS
The mean level of PMS2 protein was consistently higher in both cancer-associated benign epithelium and cancer cells of patients who recurred, compared with nonrecurrent patients. PMS2 was an independent predictor of time-to-recurrence in Cox multivariate analyses and significantly stratified patients based on outcome. PMS2 was able to improve the sensitivity of total percent Gleason 4/5 as a risk factor for recurrence in this cohort.


CONCLUSIONS
PMS2 protein levels were shown to be a predictor of time-to-recurrence after surgery. This study is the first to document that the elevation of a mismatch repair protein negatively correlates with prognosis and has implications in patient diagnosis and molecular profiling.
Norris
Alixanna M
AM
Department of Medicine, Dartmouth-Hitchcock Medical Center & Norris Cotton Comprehensive Cancer Center, Lebanon, New Hampshire, USA.
Gentry
Michael
M
Peehl
Donna M
DM
D'Agostino
Ralph
R
Scarpinato
Karin D
KD
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000601:surgery; D012189:Retrospective Studies; D015996:Survival Rate
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes