Immunohistochemical Expression of MCM2 Predicts Biochemical Recurrence in Prostate Cancer: A Tissue Microarray and Digital Imaging Analysis-Based Study of 428 Cases
Antoun Toubaji, Siobhan Sutcliffe, Alcides Chaux, Kristen Lecksell, Jessica Hicks, Angelo M De Marzo, Elizabeth A Platz, George J Netto. Johns Hopkins University, Baltimore, MD; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Washington University in Saint Louis School of Medicine, Saint Louis, MO; Georgetown University Hospital, Washington, DC
Background: Prostate cancer remains a major health problem in the United States. Established clinicopathological parameters, such as Gleason score, tumor stage and serum PSA levels, are currently the guiding tools for prognostication and disease management. Additional biomarkers that could increase accuracy of predicting disease progression, response to therapy, and survival are needed. The goal of this study was to evaluate MCM2 and Ki-67 immunoexpression as predictors of outcome in prostate cancer.
Design: 11 tissue microarrays were constructed using tumor and nontumor samples from 428 patients. Patients were divided into short-term (mean, 2.9 years) and long-term (mean, 14.1 years) follow-up groups. Endpoints were biochemical recurrence for the short-term group, and prostate cancer-related death for the long-term group. All men in the long-term follow-up group had biochemical recurrence at the time of recruitment. Tissue microarray spots were scanned and analyzed using the BLISS platform (Bacus Laboratories, Inc., Lombard, IL). MCM2 and Ki-67 levels were analyzed for i) percentage of positive cells, ii) intensity of staining, and iii) the product of percentage and intensity.
Results: Expression of both markers was higher in tumor than in nontumor glands. Percentage of MCM2 positivity was associated with Gleason score in both groups. Percentage and intensity of Ki-67 positivity were associated with Gleason score and pathologic stage only in the short-term group. Higher MCM2 percentages were associated with biochemical recurrence in the short-term group. In the long-term follow-up group, neither MCM2 nor Ki-67 levels (percentages or intensities) predicted prostate cancer death. Furthermore, no significant increase in the risk for cancer death was observed in patients with combined high MCM2 and high Ki-67 percentage expression.
Conclusions: Higher percentages of MCM2 and Ki-67 are associated with increased Gleason score. In patients treated by radical prostatectomy, high MCM2 levels are associated with biochemical recurrence. Once biochemical recurrence ensues, neither MCM2 nor Ki-67 predicts cancer-related death.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 124, Wednesday Morning