© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 916-920, Copyright © 1998 by Oxford University Press
RJ Cote, Y Shi, S Groshen, AC Feng, C Cordon-Cardo, D Skinner and G Lieskovosky
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. CONCLUSION: Levels of nuclear p27
immunoreactivity in the primary tumor can be used to predict recurrence and
survival among patients with localized prostate cancer.
ARTICLES
Association of p27Kip1 levels with recurrence and survival in patients with stage C prostate carcinoma
Department of Pathology, University of Southern California School of Medicine/Norris Comprehensive Cancer Center, Los Angeles 90033, USA. cote_r@mikey.hsc.usc.edu
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|
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|
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