Prognostic value of cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44s in surgically treated patients with prostate cancer.
OBJECTIVE
Molecular tissue markers may give the clinician additional information about patients with prostate cancer at risk for treatment failure after retropubic radical prostatectomy. We substantiate the prognostic value of 3 tissue markers, the cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44s, in addition to more conventional pathological prognosticators in an historical (before prostate specific antigen) cohort of patients with prostate cancer.


METHODS
Representative tumor sections from 92 patients who underwent retropubic radical prostatectomy were immunohistochemically stained with antibodies against p27(kip1), MIB-1 (Ki-67) and CD44s, and assessed in a semiquantitative manner. Gleason score and pathological tumor stage were recorded. All variables were correlated with clinical progression and disease specific survival on univariate and multivariate analyses.


RESULTS
On univariate analysis low (less than 50%) p27(kip1), high (10% or greater) MIB-1 and loss of CD44s expression were significantly associated with clinical outcome parameters, although MIB-1 did not reach statistical significance for disease specific survival. All 3 molecules were highly correlated with Gleason score and pathological tumor stage. Multivariate analysis showed that low p27kip1 was independent of grade and stage in predicting clinical recurrence (p <0.001) and disease specific survival (p = 0.045), while loss of CD44s was an additional independent prognostic factor for clinical recurrence (p = 0.02).


CONCLUSIONS
Reduced p27(kip1) expression is an independent predictor of poor outcome in prostate cancer, while MIB-1 is not. Decreased expression of CD44s yields additional information in predicting clinical recurrence. These tissue markers may identify patients at risk for disease recurrence after retropubic radical prostatectomy who may benefit from adjuvant therapy.
Vis
A N
AN
Department of Pathology, Josephine Nefkens Institute, Erasmus University, Rotterdam, The Netherlands.
Noordzij
M A
MA
Fitoz
K
K
Wildhagen
M F
MF
Schröder
F H
FH
van der Kwast
T H
TH
D000368:Aged; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000032:analysis*; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D018572:Disease-Free Survival; D016147:Genes, Tumor Suppressor; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D012372:ROC Curve; D012307:Risk Factors; D017211:Treatment Failure; D025521:Tumor Suppressor Proteins
D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D018960:Hyaluronan Receptors; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases