title: Value of tissue markers p27(kip1), MIB-1, and CD44s for the pre-operative prediction of tumour features in screen-detected prostate cancer.
abstract: The pre-operative prediction of prognostic tumour features in the radical prostatectomy specimen using routine clinicopathological variables remains limited. The present study evaluated the predictive value of the cell-cycle protein p27(kip1), the proliferation marker MIB-1, and the cell-adhesion protein CD44s, determined on the diagnostic needle biopsy of asymptomatic men screened for prostate cancer. Of 81 screen-detected prostate cancers, representative biopsy cores and matched radical prostatectomy specimens were immunohistochemically stained for these tissue markers. Conventional pre-operative and post-operative clinicopathological variables were assessed and cancers were divided according to a validated tumour classification model (potentially harmless, clinically significant). Low (<50%) p27(kip1) expression, high (> or = 10%) MIB-1 expression, and low (<25%) CD44s expression were considered adverse prognostic signs. Binary logistic regression analysis was performed to assess the most valuable predictors of clinically significant disease. An adverse prognostic immunostaining assessment on the biopsy was found in 10 (12.3%), 17 (21.0%), and 25 (30.9%) cases for p27(kip1), MIB-1, and CD44s, respectively. The concordance in tissue marker assessment between the biopsy specimen and matched radical prostatectomy specimens was low for all three. The positive predictive value (PPV) of p27(kip1) was 90.0%, remarkably higher than that of MIB-1 and CD44s (41.2% and 52.0%, respectively), indicating that a low radical prostatectomy p27(kip1) score is expected if the biopsy p27(kip1) score is low. Logistic regression analysis revealed that biopsy Gleason score (p<0.01) and p27(kip1) assessment (p<0.01) remained the only significant predictors of clinically significant disease. All cases with low p27(kip1) expression were found to have clinically significant disease after radical prostatectomy. The assessment of p27(kip1) in the biopsy specimen might thus assist in distinguishing between potentially aggressive and potentially non-aggressive disease in prostate cancer screening.
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus University Rotterdam, The Netherlands. vis@path.azn.nl
authors.forename: A N
authors.initials: AN
authors.lastname: Vis
authors.forename: B W G
authors.initials: BW
authors.lastname: van Rhijn
authors.forename: M A
authors.initials: MA
authors.lastname: Noordzij
authors.forename: F H
authors.initials: FH
authors.lastname: Schröder
authors.forename: Th H
authors.initials: TH
authors.lastname: van der Kwast
mesh_terms: D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D018797:Cell Cycle Proteins / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D019394:Ki-67 Antigen; D016015:Logistic Models; D008297:Male; D008403:Mass Screening / Q000379:methods*; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins / Q000032:analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000032:analysis
chemical_list: D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D018960:Hyaluronan Receptors; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D017430:Prostate-Specific Antigen