FISH and KRAS Mutation Testing as Adjuncts to Biliary Brushing Cytology for the Detection of Pancreatobiliary Tract Malignancy
Joslin M Bowen, Stanley J Radio, Dali Huang, Grant Hutchins, Julia A Bridge. University of Nebraska Medical Center, Omaha, NE
Background: ERCP with biliary brushing cytology is routinely performed for the evaluation of patients with biliary tract strictures. Although the specificity of this approach in the detection of carcinoma is nearly 100%, sensitivity rates have varied widely. Recent studies suggest molecular techniques may play a useful role in increasing the sensitivity of biliary brush cytology. The purpose of the current study was to examine the clinical value and performance characteristics of adjunctive studies to include KRAS mutation and fluorescence in situ hybridization (FISH) analysis at our institution.
Design: Based on a high clinical suspicion for malignancy, 19 specimens from 17 patients (6 female/11 male; 42-81 yrs of age) were selected for ERCP, cytologic examination, KRAS mutation testing by pyrosequencing, and copy number assessment of chromosomal loci 3, 7, 9p21, and 17 using the UroVysion FISH probe set (Abbott Laboratories). A specimen was classified as abnormal if five or more cells demonstrated polysomy; polysomy defined as gain of two or more fluorescently labeled probes to the centromeres of chromosomes 3, 7, and 17 and chromosomal band 9p21 in a single cell.
Results: All cases were negative for KRAS mutations. All 6 cases with abnormal cytologic and/or histologic findings were FISH positive (Table 1); adenocarcinoma was diagnosed in 2/6 patients following subsequent additional sampling (lymph node). A single FISH positive patient with negative cytology/histology had an elevated CA19.9 with only 2 wks clinical follow-up.
Conclusions: These data confirm the clinical utility of FISH as an adjunct to routine bile duct brushing cytology in increasing the detection of pancreatobiliary tract malignancy in patients with biliary stricture. In contrast, our KRAS findings differ from previous reports that have suggested KRAS testing in biliary brushing specimens increases cancer detection rate. However, the latter discordance could be explained at least in part by employment of different methodologic approaches with distinct mutation detection sensitivities. Interestingly, one FISH positive patient was diagnosed with biliary papillomatosis, an entity not previously subjected to molecular cytogenetic characterization.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 68, Monday Morning