PMID- 10022686
OWN - NLM
STAT- MEDLINE
DCOM- 19990311
LR  - 20151119
IS  - 0022-5347 (Print)
IS  - 0022-5347 (Linking)
VI  - 161
IP  - 3
DP  - 1999 Mar
TI  - Correlation and prognostic significance of p53, p21WAF1/CIP1 and Ki-67 expression 
      in patients with superficial bladder tumors treated with bacillus Calmette-Guerin 
      intravesical therapy.
PG  - 792-8
AB  - PURPOSE: We determine if, before intravesical bacillus-Calmette Guerin (BCG) 
      therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of 
      cell growth control, inhibiting cyclin dependent kinases) and the cell 
      proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of 
      response to BCG in patients with superficial bladder tumors. MATERIALS AND 
      METHODS: The study included 47 patients with superficial bladder tumors at high 
      risk for recurrence or progression treated with 6 weekly intravesical BCG 
      instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by 
      immunohistochemistry and the percentage of positive cells was determined in a 
      blinded fashion. Quantitative immunostaining was analyzed in relation to time to 
      recurrence and progression using univariate or multivariate analysis and the 
      Kaplan-Meier method. RESULTS: During a mean followup of 24.6 months 23 of the 47 
      patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later 
      progression to invasive disease. A p21 over expression (greater than 10%) was 
      observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but 
      not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. 
      Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that 
      p21 may also be regulated by p53 independent pathways. However, p53 did not act 
      as a predictor of recurrence or progression. In contrast, using Kaplan-Meier 
      curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were 
      associated with shorter recurrence-free survival (both p = 0.02 log rank test) 
      but they did not predict additional information about risk of progression. 
      However, multivariate analysis failed to demonstrate any independent prognostic 
      value for p21 or Ki-67 in contrast to tumor stage. CONCLUSIONS: Our results 
      indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in 
      superficial bladder cancer. The present study did not indicate an independent 
      prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or 
      Ki-67 markers. Larger prospective studies are needed to evaluate further the 
      independent value of these biological markers in superficial bladder cancer 
      management.
FAU - Zlotta, A R
AU  - Zlotta AR
AD  - Department of Urology, Erasme University Hospital, Brussels, Belgium.
FAU - Noel, J C
AU  - Noel JC
FAU - Fayt, I
AU  - Fayt I
FAU - Drowart, A
AU  - Drowart A
FAU - Van Vooren, J P
AU  - Van Vooren JP
FAU - Huygen, K
AU  - Huygen K
FAU - Simon, J
AU  - Simon J
FAU - Schulman, C C
AU  - Schulman CC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Urol
JT  - The Journal of urology
JID - 0376374
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (BCG Vaccine)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
CIN - J Urol. 1999 Mar;161(3):810-1. PMID: 10022689
MH  - Adjuvants, Immunologic/*therapeutic use
MH  - Aged
MH  - BCG Vaccine/*therapeutic use
MH  - Biomarkers, Tumor/*biosynthesis
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/*biosynthesis
MH  - Disease Progression
MH  - Enzyme Inhibitors/*metabolism
MH  - Female
MH  - Follow-Up Studies
MH  - Gene Expression Regulation, Neoplastic/*genetics
MH  - Humans
MH  - Ki-67 Antigen/*biosynthesis
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/epidemiology
MH  - Prognosis
MH  - Tumor Suppressor Protein p53/*biosynthesis
MH  - Urinary Bladder Neoplasms/*genetics/pathology/*therapy
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - S0022-5347(01)61770-1 [pii]
PST - ppublish
SO  - J Urol. 1999 Mar;161(3):792-8.