PMID- 15816547
OWN - NLM
STAT- MEDLINE
DCOM- 20050516
LR  - 20171116
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 25
IP  - 1A
DP  - 2005 Jan-Feb
TI  - Protein expression and gene copy number analysis of topoisomerase 2alpha, HER2 
      and P53 in minimally invasive urothelial carcinoma of the urinary bladder--a 
      multitissue array study with prognostic implications.
PG  - 263-71
AB  - BACKGROUND: Due to their variable clinical course, there is a need for new 
      prognostic parameters in minimally invasive (stage T1) bladder carcinomas. 
      MATERIALS AND METHODS: Using multitissue arrays, protein expression and gene copy 
      numbers of topoisomerase (TOP2alpha), HER2 and p53 were investigated by 
      immunohistochemistry and by fluorescence in situ hybridization (FISH) in 73 T1 
      tumors. The results were compared with tumor recurrence and progression. RESULTS: 
      The median TOP2alpha and p53 index was 21% (range, 3-59%) and 7% (range, 0-93%), 
      respectively. HER2 overexpression (score 3+) was detected in 9 cases (12%). High 
      TOP2alpha and p53 indices and HER2 overexpression were significantly associated 
      with earlier tumor recurrence, but not with earlier tumor progression. While 
      TOP2alpha and p53 gene amplification was detected in no case, 5 cases (8%) showed 
      HER2 gene amplification, which was related to HER2 3+ score in 4 cases. Loss of 
      TOP2alpha, HER2 and p53 gene was observed in 4 (8%), 8 (13%) and 6 cases (12%), 
      respectively. By univariate analysis, TOP2alpha index (p=0.0267), HER2 score (p 
      =0.028) and p53 index (p=0.0188) were significantly and loss of TOP2alpha gene 
      (p=0.0575) tendentially correlated with tumor recurrence, while loss of HER2 gene 
      (p=0.069) and loss of p53 gene (p=0.0587) were tendentially correlated with tumor 
      progression. In a multivariate analysis, which also included tumor grade and T1 
      substage, TOP2alpha index (p=0.043) and p53 index (p=0.02) were identified as 
      independent predictors of tumor recurrence and loss of p53 gene (p=0.012) and T1 
      substage (p=0.029) as independent predictors of tumor progression. CONCLUSION: 
      Immuno-histochemical TOP2alpha and p53 staining as well as FISH analysis of p53 
      gene copy numbers and T1 substaging are helpful means of providing additional 
      information on the biological behavior of T1 transitional cell carcinomas.
FAU - Kruger, Stefan
AU  - Kruger S
AD  - Institute of Pathology, University of Schleswig-Holstein, Lubeck, Germany. 
      krueger@patho.uni-luebeck.de
FAU - Lange, Irina
AU  - Lange I
FAU - Kausch, Ingo
AU  - Kausch I
FAU - Feller, Alfred C
AU  - Feller AC
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antigens, Neoplasm/*biosynthesis/genetics
MH  - Carcinoma, Papillary/genetics/*metabolism/pathology
MH  - DNA Topoisomerases, Type II/*biosynthesis/genetics
MH  - DNA-Binding Proteins/*biosynthesis/genetics
MH  - Female
MH  - Gene Dosage
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Receptor, ErbB-2/*biosynthesis/genetics
MH  - Tissue Array Analysis
MH  - Tumor Suppressor Protein p53/*biosynthesis/genetics
MH  - Urinary Bladder Neoplasms/genetics/*metabolism/pathology
EDAT- 2005/04/09 09:00
MHDA- 2005/05/17 09:00
CRDT- 2005/04/09 09:00
PHST- 2005/04/09 09:00 [pubmed]
PHST- 2005/05/17 09:00 [medline]
PHST- 2005/04/09 09:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 2005 Jan-Feb;25(1A):263-71.