Τίτλος:
Expression patterns of cyclins D1, E and cyclin-dependent kinase
inhibitors p21(Waf1/Cip1) and p27(Kip1) in urothelial carcinoma:
Correlation with other cell-cycle-related proteins (Rb, p53, Ki-67 and
PCNA) and clinicopathological features
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Introduction: The expression pattern of cyclins D1 and E, as well as
cyclin-dependent kinase inhibitors p21(Wa1/Cip1) and p27(Kip1) and their
relationship to tumour behaviour and patients’ prognosis was examined in
142 urothelial cell carcinomas. The expression of these proteins was
also analyzed along with other cell-cycle-related proteins such as: p53,
pRb and the proliferation-associated indices Ki-67 and proliferating
cell nuclear antigen (PCNA). Patients and Methods: These molecule
markers were localized immunochemically using the monoclonal antibodies
anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21 (4D10), and
anti-p27 (1B4) in 142 patients with urothelial cell carcinoma. Results:
Focal positivity (<10% of tumour cells) or the absence of cyclin D1
immunostaining was observed in 105/142 (73.9%) of the tumours. Cyclin
D1 expression was correlated with tumour grade and stage as well as with
the existence of in situ component. In addition, cyclin D1 expression
was positively correlated with p21(Waf1/Cip1) and p27(Kip1) and
inversely with the Ki-67 score. Focal positivity (<20% of tumour cells)
or the absence of cyclin E immunoreactivity was observed in 105/142
(73.9%) in all cases. Cyclin E expression was correlated with tumour
stage. A positive relationship between cyclin E expression and the two
associated proliferating indices Ki-67 and PCNA, as well as with p53 and
p27(Kip1) proteins expression was noted. Absence or focal positivity
(<5% of tumour cells) of p21(Waf1/Cip1) was detected in 88/142 (62%)
of the carcinomas. p21(Waf1/Cip1) expression was correlated with tumour
grade and stage. A positive relationship of its expression cyclin D1,
cyclin E, p27 and pRb expression was observed. Absence or focal
immunostaining (<20% of tumour cells) of p27 protein was detected in
55/141 (39%) in all cases. p27(Kip1) expression was correlated with
tumour grade as well as with cyclins D1 and E. The prognostic
significance of cyclins D1, E and cyclin-dependent kinase inhibitors
p21(Waf1/Cip1), p27(Kip1) in determining the risk of recurrence and
progression with both univariate ( log rank test) and multivariate (Cox
regression) methods of analysis showed no statistically significance
differences. Conclusion: These findings suggest that the level of the
cell cycle regulators studied does not seem to have a clinical value in
terms of predicting the risk of early recurrence and progression. In
addition the interrelationship probably means their contribution to the
regulation of cell growth through different pathways in bladder
carcinogenesis. Copyright (C) 2004 S. Karger AG, Basel.
Συγγραφείς:
Ioachim, E
Michael, M
Stavropoulos, NE
Kitsiou, E and
Hastazeris, K
Salmas, M
Stefanaki, S
Agnantis, NJ
Περιοδικό:
Urologia Internationalis
Λέξεις-κλειδιά:
cyclin D1; cyclin E; p21(Waf1/Cip1); p27(Kip1); p53; Rb; bladder cancer
