S. Machtens et al., Expression of the p53 and maspin protein in primary prostate cancer: Correlation with clinical features, INT J CANC, 95(5), 2001, pp. 337-342
The serine protease inhibitor Maspin has been reported to inhibit the invas
iveness and motility of prostate cancer tumor cells. Additionally, a p53-de
pendent regulatory pathway of Maspin in prostate cancer cell lines has been
indicated. The first aim of our study was to determine the prognostic valu
e of Maspin protein expression for the recurrence-free survival of patients
undergoing radical prostatectomy for the treatment of clinically localized
prostate cancer. Secondly, Maspin expression was correlated to p53 protein
expression in order to gain additional information on a possible and previ
ously suggested regulatory influence of the wild-type p53 protein on the Ma
spin protein expression. Tumor specimens obtained from 84 patients undergoi
ng radical prostatectomy for localized prostate cancer were investigated fo
r the expression of the Maspin and p53 protein by an immunohistochemic appr
oach. Maspin protein expression was correlated with further patients' and t
umor characteristics such as tumor stage, histologic grading, regional lymp
h node status, p53 protein expression and recurrence-free survival of the p
atients following radical prostatectomy. After a median follow-up of 64 mon
ths (24-197 months), 23 of 40 patients (58%) with a negative or decreased M
aspin expression (group I) developed local recurrence or systemic tumor pro
gression in contrast to 8 of 44 patients (18%) with a retained expression o
f the Maspin protein (group 2) (p = 0.02; log-rank test). The median recurr
ence-free survival following radical prostatectomy was 26 months (12-37 mon
ths) for group I patients and 41 months (5-134 months) for patients from gr
oup 2 (p = 0.04). A positive immunohistochemic staining reaction for the p5
3 protein was significantly correlated with a decreased expression of the M
aspin protein (p = 0.015; Spearman correlation coefficient). Additionally,
loss of Maspin protein expression was correlated to higher tumor stages (p
= 0.002) and an increasing histologic dedifferentiation (p = 0.03). This is
the first study to indicate that Maspin protein possibly functions as a cl
inically relevant inhibitor of tumor progression, preventing the local inva
siveness and further systemic progression of prostate cancer. Our investiga
tion delivers first hints for a p53-dependent regulatory pathway of the Mas
pin protein in human prostate cancer. (C) 2001 Wiley-Liss, Inc.