title: Immunohistochemical expression of minichromosome maintenance complex protein 2 predicts biochemical recurrence in prostate cancer: a tissue microarray and digital imaging analysis-based study of 428 cases.
abstract: Prostate cancer remains a major health problem in the United States. Established clinicopathologic parameters such as Gleason score, T stage, and prostate-specific antigen levels are currently the guiding tools for prognostication and disease management. The addition of biomarkers could increase the accuracy of these parameters for predicting disease progression, response to therapy, and survival. In this regard, the goal of this study was to evaluate minichromosome maintenance complex protein 2 and Ki-67 immunohistochemical expression as predictors of outcome in prostate cancer. For this purpose, 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. End points were biochemical recurrence for the short-term follow-up group and prostate cancer-related death for the long-term follow-up group. All men in the long-term follow-up group had biochemical recurrence at the time of recruitment. Expression of both markers was higher in tumor than in nontumor glands. Percentage of minichromosome maintenance complex protein 2 was associated with Gleason score in both groups. Percentage of Ki-67 was associated with Gleason score and pathologic stage only in the short-term follow-up group. Higher minichromosome maintenance complex protein 2 percentages were associated with biochemical recurrence in the short-term follow-up group. In the long-term follow-up group, neither minichromosome maintenance complex protein 2 nor Ki-67 levels predicted prostate cancer death. In conclusion, our results suggest that in patients treated by radical prostatectomy for clinically localized prostate cancer, immunohistochemistry for minichromosome maintenance complex protein 2 expression could be used to predict biochemical recurrence, independent of other known clinicopathologic factors.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Antoun
authors.initials: A
authors.lastname: Toubaji
authors.forename: Siobhan
authors.initials: S
authors.lastname: Sutcliffe
authors.forename: Alcides
authors.initials: A
authors.lastname: Chaux
authors.forename: Kristen
authors.initials: K
authors.lastname: Lecksell
authors.forename: Jessica
authors.initials: J
authors.lastname: Hicks
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003131:Combined Modality Therapy; D018450:Disease Progression; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D019394:Ki-67 Antigen / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D017430:Prostate-Specific Antigen; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2