Affiliations: [a] Division of Urology, Duke University Medical Center, Durham, NC, USA | [b] Department of Urology, University of Illinois Chicago, Chicago, IL, USA | [c] Division of Urology, Urology of Virginia, Hampton, VA, USA | [d] Department of Pathology, Duke University Medical Center, Durham, NC, USA
Correspondence:
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Corresponding author: Michael R. Abern, Department of Urology, University of Illinois Chicago, 820 South Wood Street Suite 515, Chicago, IL 60612, USA. Tel.: +1 312 996 9330; E-mail:[email protected]
Abstract: BACKGROUND: Abnormal methylation of urinary TWIST1 and NID2
conferred high sensitivity and specificity for the detection of urothelial
carcinoma. OBJECTIVE: We examine the performance of the urine-based
TWIST1/NID2 methylation assay with the addition of urine cytology for the
detection of urothelial carcinoma. MATERIALS AND METHODS: A
prospective multi-institutional study was conducted to assess the
performance of a methylation assay for patients with hematuria or under
surveillance for non-muscle invasive bladder cancer (NMIBC). All patients
underwent cystoscopy, a methylation assay, and cytology. Receiver operator
characteristic (ROC) curves were constructed for cytology alone, the
methylation assay alone, and a combined model. Areas under the curve (AUC)
were compared using likelihood ratio tests. RESULTS: A total of 172
patients were enrolled (37% for hematuria and 63% NMIBC). The AUC for
cytology alone with equivocal cytologies positive was 0.704, and improved to
0.773 with the addition of the DNA methylation assay (p < 0.001). When the
equivocal cytologies were considered negative, the AUC improved from 0.558
to 0.697 with the addition of the DNA methylation assay (p = 0.003). CONCLUSIONS: Addition of a TWIST1/NID2-based DNA methylation assay
adds diagnostic value to urine cytology and the model is sensitive to the
classification of equivocal cytology.
