Gene expression profiling of progressive papillary noninvasive carcinomas of the urinary bladder.
OBJECTIVE
The aim of the present study was to define gene expression profiles of noninvasive and invasive bladder cancer, to identify potential therapeutic or screening targets in bladder cancer, and to define genetic changes relevant for tumor progression of recurrent papillary bladder cancer (pTa).


METHODS
Overall, 67 bladder neoplasms (46 pTa, 3 pTis, 10 pT1, and 8 pT2) and eight normal bladder specimens were investigated by a combination of laser microdissection and gene expression profiling. Eight of 16 patients with recurrent noninvasive papillary bladder tumors developed carcinoma in situ (pTis) or invasive bladder cancer (> or = pT1G2) in the course of time. RNA expression results of the putative progression marker cathepsin E (CTSE) were confirmed by immunohistochemistry using high-throughput tissue microarray analysis (n = 776). Univariate analysis of factors regarding overall survival, progression-free survival, and recurrence-free survival in patients with urothelial bladder cancer was done.


RESULTS
Hierarchical cluster analyses revealed no differences between pTaG1 and pTaG2 tumors. However, distinct groups of invasive cancers with different gene expression profiles in papillary and solid tumors were found. Progression-associated gene profiles could be defined (e.g., FABP4 and CTSE) and were already present in the preceding noninvasive papillary tumors. CTSE expression (P = 0.003) and a high Ki-67 labeling index of at least 5% (P = 0.01) were the only factors that correlated significantly with progression-free survival of pTa tumors in our gene expression approach.


CONCLUSIONS
Gene expression profiling revealed novel genes with potential clinical utility to select patients that are more likely to develop aggressive disease.
Wild
Peter J
PJ
Institute of Pathology, University of Regensburg, Regensburg, Germany.
Herr
Alexander
A
Wissmann
Christoph
C
Stoehr
Robert
R
Rosenthal
Andre
A
Zaak
Dirk
D
Simon
Ronald
R
Knuechel
Ruth
R
Pilarsky
Christian
C
Hartmann
Arndt
A
D000368:Aged; D000704:Analysis of Variance; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020059:Cathepsin E / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D020059:Cathepsin E