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Mutation Profile and Fluorescence In Situ Hybridization Analyses Increase Detection of Malignancies in Biliary Strictures

Gonda TA, Viterbo D, Gausman V, et al.
Clin Gastroenterol Hepatol. 2017;15:913-919.

Detecting malignancies in biliary strictures can pose many challenges. This prospective study evaluated the combined accuracy of fluorescence in situ hybridization (FISH) and polymerase chain reaction-based DNA mutation profiling of specimens collected using standard brush techniques in consecutive patients treated for biliary strictures by endoscopic retrograde cholangiopancreatography (n=107).

Routine cytology and FISH analyses on cells collected by standard brush techniques were performed. Additionally, supernatants were analyzed for point mutations in KRAS and loss-of-heterozygosity mutations in tumor-suppressor genes at 10 loci. Strictures were determined to be nonmalignant based on repeat image analysis or laboratory test results 12 months after the procedure. Malignant strictures were identified based on subsequent biopsy or cytology analyses, pathology analyses of samples collected during surgery, or death from biliary malignancy.

Cytology analysis identified patients with malignancies with 32% sensitivity and 100% specificity. Addition of FISH or mutation profiling results to cytology results increased the sensitivity of detection to 51% (P<.01) without reducing specificity. The combination of cytology, mutation profiling, and FISH analyses detected malignancies with 73% sensitivity (P<.001). FISH and mutation profiling together identified 17 of the 28 malignancies not detected by cytology analysis; FISH identified an additional 9 of the 28 malignancies and mutation profiling identified an additional 8 malignancies. (These techniques can be performed using standard brush samples collected during endoscopic retrograde cholangiopancreatography, with mutations detected in free DNA in supernatant fluid of samples.)

The addition of FISH and mutation analyses to cytology analysis significantly increased the level of
sensitivity with which we detected malignancy in biliary strictures, with 100% specificity.

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