Microarray gene expression profiling and analysis of bladder cancer supports the sub-classification of T1 tumours into T1a and T1b stages.
OBJECTIVE
To try and identify a molecular signature for pathological staging and/or grading. through microarray analysis.


METHODS
We performed a prospective multicentre study between September 2007 and May 2008 that included 108 bladder tumours (45 pTa, 35 pT1 and 28>pT1). Microarray analysis was performed using Agilent Technologies Human Whole Genome 4 × 44K oligonucleotide microarrays (Agilent, Santa Clara, CA, USA). A 'dual colour' method was used vs a reference pool of tumours. From the lists of genes provided by the Biometric Research Branch class comparison analyses, we validated the microarray results of 38 selected differentially expressed genes using reverse transcriptase quantitative PCR in another bladder tumour cohort (n = 95).


RESULTS
The cluster 'superficial vs invasive stage' correctly classified 92.9% of invasive stages and 66.3% of superficial stages. Among the superficial tumours, the cluster analysis showed that pT1b tumours were closer to invasive stages than pT1a tumours. We also found molecular differences between low and high grade superficial tumours, but these differences were less well defined than the difference observed for staging.


CONCLUSIONS
We confirmed that the histopathological classification into subgroups pTa, pT1a and pT1b can be translated into a molecular signature with a continuous progression of deregulation (overexpression or repression of these genes) from superficial (pTa) to more invasive (pT1a then b) stages.
Service de Biochimie Biologie Moléculaire, Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud, Pierre Bénite, France.
Françoise
F
Descotes
Philippe
P
Dessen
Pierre Paul
PP
Bringuier
Myriam
M
Decaussin
Pierre Marie
PM
Martin
Marjorie
M
Adams
Arnauld
A
Villers
Eric
E
Lechevallier
Xavier
X
Rebillard
Claire
C
Rodriguez-Lafrasse
Marian
M
Devonec
Philippe
P
Paparel
Paul
P
Perrin
Vladimir
V
Lazar
Alain
A
Ruffion
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*
D014408:Biomarkers, Tumor
bladder; carcinoma; invasive; microarray; pT1a stage; pT1b stage; superficial