Association of p27Kip1 levels with recurrence and survival in patients with stage C prostate carcinoma.
BACKGROUND
There are few biologic determinants that are prognostic for patients with localized prostate cancer. We examined whether cellular levels of the cyclin-kinase inhibitor p27Kip1 (also known as p27) in prostate tumors could be used to predict progression of this disease.


METHODS
Levels of p27 in tumor cell nuclei were assessed by immunohistochemical analysis of tissue sections from the primary tumors of 96 patients with stage C prostate carcinoma who had been treated by radical prostatectomy. Tumors were classified into one of the following three groups on the basis of the percentage of tumor cells showing nuclear p27 reactivity: low (0%-10%), moderate (11%-50%), and high (>50%). The Mantel-Haenszel test, Kaplan-Meier analysis, and the logrank test were used to calculate the probability that nuclear p27 levels were associated with tumor grade and substage, with a serum prostate-specific antigen (PSA) recurrence (defined as the finding of a detectable level [0.4 ng/mL or greater] of serum PSA following radical prostatectomy), with the recurrence of clinically evident disease, and with survival. All reported P values are two-sided.


RESULTS
Luminal cells and basal cells of normal prostate glands showed high levels of nuclear p27 immunoreactivity in all tissue sections examined. Fifty-three tumors showed high p27 reactivity, 31 showed moderate reactivity, and 12 showed low or no detectable reactivity. Decreased levels of p27 were associated with tumor grade (P = .004). Tumor levels of p27 were not associated with preoperative prostate-specific antigen levels (P = .360) or with tumor substage (P = .320). However, decreased p27 reactivity was significantly associated with an increased probability of recurrence (P = .004) and decreased survival (P = .010). The median recurrence-free interval for patients with tumors showing high, moderate, or low p27 reactivity was 13.7 years, 8.4 years, and 4.7 years, respectively. Median survival times were more than 14 years, more than 13.5 years, and 8.1 years for patients in the high, moderate, and low p27 reactivity groups, respectively.


CONCLUSIONS
Levels of nuclear p27 immunoreactivity in the primary tumor can be used to predict recurrence and survival among patients with localized prostate cancer.
Cote
R J
RJ
Department of Pathology, University of Southern California School of Medicine/Norris Comprehensive Cancer Center, Los Angeles 90033, USA. cote_r@mikey.hsc.usc.edu
Shi
Y
Y
Groshen
S
S
Feng
A C
AC
Cordon-Cardo
C
C
Skinner
D
D
Lieskovosky
G
G
D000368:Aged; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases