Integration of Morphology with Fluorescent In Situ Hybridization (FISH) Increases the Accuracy of Bladder Cancer Diagnosis in Standard Papanicolaou (PAP) Urine Cytology: Evaluation of Chromosome Tetrasomy in Urothelial Carcinoma
YX Liu, L Hutchinson, M St.Cyr, J Garver, B Woda, EF Cosar. UMass Memorial Medical Center, Worcester, MA
Background: UroVysion FISH is routinely used to detect bladder cancer. FDA-approved criteria for a positive result are defined as chromosome (CHR) polysomy (POLY) in 4 cells. By definition this includes tetrasomy (TET), a natural product of cell division, which is a common factor leading to false positive results. Therefore, we evaluated the utility of separate POLY and TET categories, using published thresholds (TET 4, 10, and 10%), or a combined assay integrating cytomorphology and FISH (CM-FISH), to increase test accuracy.
Design: 133 cases of urine cytology with a PAP-stained slide and associated biopsy were selected. Cytological review resulted in 22 negative, 75 atypical, 25 suspicious and 11 positive diagnoses. 63 cases showed no tumor on biopsy. 43 cases were low-grade and 27 were high-grade by the WHO/ISUP criteria. Urothelial cells with atypical cytological features were subjected to CM-FISH using Duet/Solo Automated Imaging System. TET was defined as 4 copies of CHR 3, 7, 17, 9p21, with up to one missing probe signal (e.g. 4, 3, 4, 4).
Results: The FDA scoring criteria yielded a sensitivity of 84.3% and specificity of 55.6%. Excluding normal cells in the CM-FISH caused a modest reduction in sensitivity to 77.1%, but a marked increase in specificity to 84.1%. Removing TET from the POLY class reduced sensitivity to 67.1% and increased specificity to 71.4%. A separate analysis of cases with <4 POLY cells, showed TET 4, 10 or 10% accounted for 30.4% or 17.4% of positive biopsies. Using CM-FISH with TET 10 increased sensitivity to 34.8% and gave a specificity of 97.8% in the same analysis.
NA= not applicable
|Category||POLY+TET||POLY||TET||TET (exclude POLY 4)|
|Threshold|| 4|| 4|| 10|| 4|| 10 ( 10%)|| 10|
|Total case #||133||133||133||133||68||68||68|
Conclusions: Excluding TET from FDA approved criteria increases specificity but at a cost in sensitivity. Based on our data, we recommend using CM-FISH to achieve the highest specificity without losing sensitivity. As criteria for positive FISH, TET alone has a limited value.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 63, Monday Morning