Diagnostic value of K-ras mutation analysis for pancreaticobiliary cytology specimens with indeterminate diagnosis§


  • Presented in part at the 98th Annual Meeting of the United States and Canadian Academy of Pathology; March 7-13, 2009; Boston, Massachusetts.

  • Fredilyn M. Lipata received the 2009 Research Award from the Papanicolaou Society of Cytopathology.

  • §

    This study received the 2009 Research Award from the Papanicolaou Society of Cytopathology (to Fredilyn M. Lipata).



Fine-needle aspiration and bile duct brushing cytology have been traditionally used for early detection of pancreaticobiliary malignancy. Quite frequently, the cytological interpretations of these specimens are indeterminate. In this retrospective study, we evaluated the diagnostic value of detecting K-ras (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation in pancreaticobiliary cytology specimens that had equivocal cytological diagnoses.


A total of 129 cases that had indeterminate cytology diagnoses, K-ras mutational analysis, and histopathological follow-up were retrieved. The cytological interpretations, histopathological diagnoses, and K-ras mutation results were reviewed and analyzed.


Overall, the sensitivity and specificity of K-ras mutation for detection of pancreaticobiliary malignancy including adenocarcinoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm were 57% and 94%, respectively. The positive and negative predictive values of K-ras mutation for the presence of pancreaticobiliary malignancy were 94% and 60%, respectively.


The results demonstrate that K-ras mutation has a high predictive value for malignancy in patients with indeterminate pancreaticobiliary cytology and should be included as an important adjuvant diagnostic marker. It should be noted that a negative K-ras mutation result does not rule out malignancy, and K-ras mutation can be detected, although infrequently, in morphologically benign conditions. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society.