TGF-betaRII, BAX, IGFIIR, caspase-5, hMSH3 and hMSH6 alterations are not associated with microsatellite instability or p53 mutations in invasive urothelial carcinoma of the urinary bladder.
OBJECTIVE
The aim of this study was to determine the potential synchronous contribution of alterations in TGF-betaRII, BAX, IGFIIR, caspase-5, hMSH3 and hMSH6 genes to the development and clinical outcome of bladder cancer, in relation to p53 mutations, microsatellite status and hMLH1/hMSH2 expression.


METHODS
Molecular biology techniques as well as immunohistochemistry were applied in 69 samples from patients with urothelial carcinoma.


RESULTS
Microsatellite alterations were observed in TGF-betaRII(A)(10 )(16%) and BAX(G)(8 )(3%), irrespective of the presence of p53 mutations, but not in IGFIIR(G)(8), caspase-5(A)(10, ) hMSH3(A)(8) and hMSH6(C)(8). A statistically significant correlation could be found only between hMLH1 expression and the presence of microsatellite instability (Fisher's exact test, p = 0,013). Survival analysis indicated that apart from grade and T-category, hMLH1 expression was the only parameter significantly affecting overall survival (p = 0.021 in univariate and p = 0.015 in multivariate analysis) and recurrence-free survival (p = 0.0463 in univariate and p = 0.022 in multivariate analysis).


CONCLUSIONS
We conclude that alterations of the examined target genes of MSI are rare in urinary bladder carcinoma and they are not associated with microsatellite instability or the presence of p53 mutations.
Saetta
Angelica A
AA
Department of Pathology, Medical School, National and Kapodistrian University of Athens, Greece. asaetta@med.uoa.gr
Korkolopoulou
Penelope
P
Karlou
Maria
M
Levidou
Georgia
G
Goudopoulou
Athina
A
Thymara
Irene
I
Stamatelli
Angeliki
A
Tzivras
Michalis
M
Michalopoulos
Nikolaos V
NV
Thomas-Tsagli
Euphemia
E
Patsouris
Efstratios
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D015999:Multivariate Analysis; D000074081:MutS Homolog 3 Protein; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein; D017527:Receptor, IGF Type 2; D018125:Receptors, Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; C099217:CASP5 protein, human; D020169:Caspases