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Clinical Value of K-ras Codon 12 Analysis and Endobiliary Brush Cytology for the Diagnosis of Malignant Extrahepatic BileDuct Stenosis¹

Departments of Pathology [P. D. J. S., E. C., T. B. R., L. A. N., G. J. A. O.] and Gastroenterology [E. A. J. R., K. H.] Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; and Departments of Pathology [R. H. H.] and Oncology [R. H. H.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205

Extrahepatic biliary stenosis can be caused by benign and malignant disorders. In most cases, a tissue diagnosis is needed for optimal management of patients, but the sensitivity of biliary cytology for the diagnosis of a malignancy is relatively low. The additional diagnostic value of K-ras mutational analysis of endobiliary brush cytology was assessed. Endobiliary brush cytology specimens obtained during endoscopic retrograde cholangiopancreaticography were prospectively collected from 312 consecutive patients with extrahepatic biliary stenosis. The results of conventional light microscopic cytology and K-ras codon 12 mutational analysis were compared and evaluated in view of the final diagnosis made by histological examination of the stenotic lesion and/or patient follow-up. The sensitivities of cytology and mutational analysis to detect malignancy were 36 and 42%, respectively. When both tests were combined, the sensitivity increased to 62%. The specificity of cytology was 98%, and the specificity of the mutational analysis and of both tests combined was 89%. Positive predictive values for cytology, mutational analysis, and both tests combined were 98, 92, and 94%, whereas the corresponding negative predictive values were 34, 34, and 44%, respectively. The sensitivity of K-ras mutational analysis was 63% for pancreatic carcinomas compared to 27% for bile duct, gallbladder, and ampullary carcinomas. K-ras mutational analysis can be considered supplementary to conventional light microscopy of endobiliary brush cytology to diagnose patients with malignant extrahepatic biliary stenosis, particularly in the case of pancreatic cancer. The presence of a K-ras codon 12 mutation in endobiliary brush cytology per se supports a clinical suspicion of malignancy, even when the conventional cytology is negative or equivocal.

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