DIAGNOSTIC PERFORMANCE OF FLUORESCENCE IN SITU HYBRIDIZATION (FISH) FOR BILIARY STRICTURES: DOES THE DEFINITION MATTER?

Introduction: Standard brush cytology has poor sensitivity for detecting malignancy in biliary strictures. Fluorescence in situ hybridization (FISH) has been reported as a useful adjunctive test in evaluation of biliary strictures. However, the diagnostic performance and definitions of a positive FISH result vary across different studies. This meta-analysis aimed to define the diagnostic performance of FISH in evaluation of biliary strictures.
Methods: A systematic search of Ovid MEDLINE, EMBASE, Cochrane and Scopus databases was conducted by an expert librarian through July 2023. Studies reporting the diagnostic performance of UroVysion®(Abbott Molecular) probe set in adult patients (>18y age) with biliary strictures were included. Sensitivity analysis of studies using (1) only polysomy (>2 copies of ≥2 probes) and (2) polysomy and tetra/trisomy as criteria for positive FISH test were also performed. Bivariate random-effects model was used to summarize the results from individual studies while keeping the two-dimensionality of the data. Receiver operating characteristic curves (ROC) were constructed using a hierarchical summary. Results were reported as sensitivity (Sn), specificity (Sp), positive and negative likelihood ratio (LR). All statistical analyses were performed using the R-software. Results are presented as point estimate (95% confidence interval [CI]).
Results: A total of 17 studies with 1042 FISH specimens were included. Malignancy was identified in 596 (57.2%) cases.. A positive FISH (as defined by the study authors) had a pooled Sn of 56.7% (49.2-63.8%, I²=19.3%) and Sp of 86.5% (76.7-92.5%, I²=19.3%). Negative FISH had a small magnitude of change (negative LR=0.5 [0.4-0.6]) whereas a positive FISH resulted in a moderate magnitude of change in probability of diagnosis (positive LR=4.4 [2.5-7.2]) after testing. Pooled false positive rate was 13.5% (7.5-23.3%, I²=19.3%). Performance of FISH was similar amongst studies with primary sclerosing cholangitis (PSC, n=3). In PSC, pooled FISH Sn was 56.2% (28.3-80.6%, I²=0%) and Sp was 87.5% (46.0-94.5%, I²=0%)

On sensitivity analysis of studies using only FISH polysomy as considered positive (n=9), FISH Sn (50.1%, 44.5-55.7%, I²=18%) was similar however the Sp increased to 94.5% (89.3-97.2%, I²=18%). In those studies that considered tetrasomy/trisomy in addition to polysomy as positive (n=8), FISH Sn increased significantly to 65.1% (57.7%-71.8% I²=0%), however Sp dropped significantly to 75.7% (60.4.-86.4%, I²=0%).

Conclusions: Overall FISH testing for detecting malignancy in biliary strictures has a pooled sensitivity of 55.9% and specificity of 88.1%. These test characteristics are impacted by the definition of a positive test. Reporting of FISH testing requires further standardization to avoid false positive test results.