TY - JOUR
TI - Prognostic implications of aberrations in p16/pRb pathway in urothelial
bladder carcinomas: A multivariate analysis including p53 expression and
proliferation markers
AU - Korkolopoulou, P
AU - Christodoulou, P
AU - Lazaris, A
AU - Thomas-Tsagli,
AU - E
AU - Kapralos, P
AU - Papanikolaou, A
AU - Kalliteraki, I
AU - Davaris, P
JO - European Urology
PY - 2001
VL - 39
TODO - 2
SP - 167-177
PB - Karger
SN - 0302-2838, 1873-7560
TODO - 10.1159/000052432
TODO - urothelial carcinoma; p16; pRb; p53
TODO - Objective: To assess the prognostic value of the expression of two
negative regulators of the cell cycle, namely CDKN2/INK4a gene product
(p16) and retinoblastoma gene product (pRb), in urinary bladder cancer
in relation to clinicopathological parameters, proliferative fraction
and p53 protein accumulation.
Methods: Paraffin sections from 139 patients with urothelial carcinomas
were stained immunohistochemically with antibodies to p16 (F12), pRb
(PMG3-245), p53 (DO1), PCNA (PC10) and Ki-67 (MIB-1).
Results: Diminished p16 and pRb expression occurred in 29 and 74% of
cases, respectively, being associated with advanced stage but not with
histological grade, papillary status or proliferation rate. In most
cases (53%) with some fault in the p16/pRb pathway, only one gene was
affected. A double-negative p16/pRb phenotype was comparatively uncommon
(25%) and was usually seen in T3-T4 tumours. In survival analysis
(either univariate or multivariate) aberrant p16 expression was an
adverse prognostic parameter only in T3-T4 tumours. In contrast, the
abnormal p16/pRb and p53/p16 phenotypes were linked to a diminished
overall and disease-free survival (univariate analysis); p53/p16
abnormal expression was also found to be an independent predictor of
reduced survival in muscle-invasive tumours, while proliferation markers
were the only parameters with independent significance in superficial
(Ta-T1) tumors.
Conclusion: Our results suggest that lack of p16 immunoexpression, when
combined with p53 accumulation plays an important role in determining
the clinical outcome in muscle-invasive urothelial carcinomas. Copyright
(C) 2001 S. Karger AG, Basel.
ER -