Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is a useful tool in the diagnosis of pancreatic masses. Genetic analysis of these samples could increase the sensitivity and specificity of diagnosis. This study aimed to evaluate the usefulness of a novel method for the detection of mutations in theKRAS(Kirsten rat sarcoma-2 virus) gene for the diagnosis of pancreatic cancer.
EUS-FNABs were performed on 82 patients with pancreatic masses, including 54 cases of pancreatic ductal adenocarcinoma and 28 of non-malignant pancreatic masses. The biopsies were histopathologically and cytopathologically evaluated, and the detection ofKRASgene mutations (codons 12 and 13) was performed through peptide nucleic acid-directed polymerase chain reaction clamping and DNA sequencing.
In the pancreatic cancer cases, 88.9% (48/54; 95% confidence interval (CI): 80.5–97.2%) hadKRASmutations, while 61.1% (33/54; 95% CI: 48.1–74.1%) were unequivocally diagnosed by histo/cytopathology. In the indeterminate patients (n=49; diagnosed by EUS-FNA as either insufficient material to make a diagnosis, no malignancy, or suspicion of malignancy), there were 10 cases of pancreatic cancer with low serum carbohydrate antigen 19-9 (CA19-9) (<37 U/l) and 6 of these wereKRASmutations. The sensitivity of detection byKRASmutations (76.2%) and the combination ofKRASmutations and serum CA19-9 (81%) were significantly higher than for serum CA19-9 alone (52.4%). A logistic regression model showed that theKRASmutation was significant (odds ratio=5.830; CI: 1.531–22.199,P=0.01), but not serum CA19-9. In the non-malignant pancreatic masses (n=28),KRASmutations were detected in nine precancerous lesions.
Our method for the detection ofKRASgene mutations may be useful to supplement histo/cytopathologic evaluations for pancreatic cancer, and is superior to serum CA19-9 in EUS-FNAB histo/cytopathology-indeterminate patients. Results warrant further verification in other patient populations.
1Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
2These authors contributed equally to this work
Correspondence: ZhaoShen Li, MD, PhD, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China. E-mail: firstname.lastname@example.org
published online 30 August 2011
Received 30 July 2010; accepted 27 July 2011