The Elevated Expression of a Mismatch Repair Protein Is a Predictor for Biochemical Recurrence After Radical Prostatectomy

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 18; no. 1; pp. 57 - 64
• Main Authors: MORRIS, Alixanna M, GENTRY, Michael, PEEHL, Donna M, D'AGOSTINO, Ralph, SCARPINATO, Karin D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.01.2009
• Subjects: Adenosine Triphosphatases - metabolism; Adult; Aged; Biological and medical sciences; Biomarkers, Tumor - metabolism; clinical biomarker; DNA Mismatch Repair; DNA Repair Enzymes - metabolism; DNA-Binding Proteins - metabolism; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; mismatch repair; Mismatch Repair Endonuclease PMS2; Neoplasm Recurrence, Local - metabolism; PMS2; Predictive Value of Tests; Prognosis; Proportional Hazards Models; prostate cancer; Prostatectomy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - surgery; Retrospective Studies; risk factor; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the genital tract and mammary gland; Survival Rate; Tumors; Human; Urinary system disease; Prognosis; Prostate disease; Malignant tumor; Gene expression; Biochemical recurrence; Urology; Cancerology; Base mismatching; Treatment; Surgery; Genetics; Prostatectomy; Male genital diseases; Prostate cancer; Cancer
• DOI: 10.1158/1055-9965.EPI-08-0377
• ISSN: 1055-9965

Purpose: 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. Experimental Design: 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. (Cancer Epidemiol Biomarkers Prev 2009;18(1):57–64)