One-year monitoring of an oligonucleotide fluorescence in situ hybridization probe panel laboratory-developed test for bladder cancer detection.
BACKGROUND
Previously, we had developed and manufactured an oligonucleotide fluorescence in situ hybridization (OligoFISH) probe panel based on the most clinically sensitive chromosomes found in a reference set of bladder carcinoma cases. The panel was clinically validated for use as a diagnostic and monitoring assay for bladder cancer, reaching 100% correlation with the results of the UroVysion test. After 1 year of using this probe panel, we present here the comparison of cytology, cystoscopy, and pathology findings to the OligoFISH probe panel results to calculate its clinical performance.


METHODS
In order to calculate clinical performance, we compared the OligoFISH results to the cytology and cystoscopy/pathology findings for 147 initial diagnoses and 399 recurrence monitorings. Finally, we compared clinical performance to published values for the UroVysion test, including both low- and high-grade tumors.


RESULTS
Chromosomes 3, 6, 7, and 20 were highly involved in bladder carcinoma aneuploidy. At the initial diagnosis, we obtained 90.5% (95% confidence interval [CI]: 84.5%-94.7%) accuracy, 96.8% sensitivity (95% CI: 91.0%-99.3%), 79.2% specificity (95% CI: 65.9%-87.8%), 89.2% positive predictive value (PPV; 95% CI: 81.5%-94.5%), and 93.3% negative predictive value (NPV; 95% CI: 81.7%-97.3%). When monitoring for recurrence, we obtained 85.2% accuracy (95% CI: 81.3%-88.5%), 82.0% sensitivity (95% CI: 76.0%-87.1%), 88.4% specificity (95% CI: 83.2%-92.5%), 87.7% PPV (95% CI: 82.1%-92.0%), and 83.0% NPV (95% CI: 77.3%-87.8%). When looking at low- and high-grade tumors, the test showed 100% sensitivity for high-grade tumors (95% CI: 92.5%-100%) and 87.5% sensitivity (95% CI: 68.8%-95.5%) for low-grade tumors. All the clinical parameters for the OligoFISH panel were higher than the UroVysion test's published performance. We found significantly higher clinical sensitivity and NPV at initial diagnosis and significantly higher specificity and PPV for recurrence.


CONCLUSIONS
The OligoFISH probe panel is a fast, easy, and reproducible test for bladder cancer diagnosis and monitoring, with excellent clinical performance and utility.
Michigan Institute of Urology, St Claire Shores, MI, USA.
Rima
R
Tinawi-Aljundi
Cellay, Inc., Cambridge, MA, USA.
Lauren
L
King
Cellay, Inc., Cambridge, MA, USA.
Shannon T
ST
Knuth
Cellay, Inc., Cambridge, MA, USA.
Michael
M
Gildea
Cellay, Inc., Cambridge, MA, USA.
Carrie
C
Ng
Cellay, Inc., Cambridge, MA, USA.
Josh
J
Kahl
Cellay, Inc., Cambridge, MA, USA.
Jacqueline
J
Dion
Cellay, Inc., Cambridge, MA, USA.
Chris
C
Young
Michigan Institute of Urology, St Claire Shores, MI, USA.
Edward W
EW
Schervish
Michigan Institute of Urology, St Claire Shores, MI, USA.
J Rene
JR
Frontera
Michigan Institute of Urology, St Claire Shores, MI, USA.
Jason
J
Hafron
Michigan Institute of Urology, St Claire Shores, MI, USA.
Kenneth M
KM
Kernen
Michigan Institute of Urology, St Claire Shores, MI, USA.
Robert
R
Di Loreto
Cellay, Inc., Cambridge, MA, USA.
Joan
J
Aurich-Costa
FISH; UroVysion; bladder neoplasm; urologic oncology