A methylation assay for the detection of non-muscle-invasive bladder cancer (NMIBC) recurrences in voided urine.
BJU Int
; 109(6): 941-8, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-21756281
ABSTRACT
OBJECTIVE:
To develop a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay for the detection of non-muscle invasive bladder cancer (NMIBC) recurrences in voided urine. PATIENTS ANDMETHODS:
Genes frequently methylated in NMIBC tumours (n= 37) were selected to develop a BC-specific MS-MLPA assay. Genes methylated in blood from patients with BC (n= 29) and genes methylated in urine from patients with no history of BC (n= 46) were excluded. A four-gene panel with the highest predictive value was selected from the initial assay. This four-gene panel was tested and validated on urine from patients with a histologically confirmed recurrence (n= 68 test set; n= 49 validation set) and urine samples from patients without BC (n= 91, test set) and urine from recurrence-free BC (rec-free BC) patients (n= 60, validation set). A model was developed to predict the probability of having a recurrence based on methylation of the four-gene panel and a threshold probability with the highest sensitivity and specificity was determined. The outcome of the model was validated on BC urine samples (n= 65) and on urine samples from rec-free BC patients (n= 29).RESULTS:
The BC MS-MLPA assay consisted of 23 methylation probes. The selected four-gene panel included APC_a, TERT_a, TERT_b, and EDNRB. This panel reached an area under the receiver operating characteristic curve (AUC) of 0.82 (test set) and AUC 0.69 (validation set). Sensitivity and specificity for the detection of a concomitant tumour were 63.3% and 58.3% respectively (test set) and 72.3% and 55.2%, respectively (validation set).CONCLUSIONS:
We have developed a methylation detection assay specifically for the detection of recurrences in patients with NMIBC in voided urine. The findings are promising and improvement of this test could eventually contribute to a more individualized patient friendly surveillance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Urina
/
Bioensaio
/
Neoplasias da Bexiga Urinária
/
Recidiva Local de Neoplasia
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
/
Aged
/
Aged80
/
Humans
/
Middle aged
Idioma:
En
Revista:
BJU Int
Assunto da revista:
UROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Holanda