KRAS in Cyst Fluid Obtained by Endoscopic Ultrasound–Fine-Needle Aspiration in Pancreatic Cystic Lesions

Abstract

To evaluate the diagnostic accuracy of KRAS mutation in pancreatic cystic fluid and compare it with carcinoembryonic antigen and cytology, we identified studies with cyst fluid obtained by endoscopic ultrasound prior to surgery. We classified cysts as malignant, premalignant, and benign. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic curve analysis were conducted. We analyzed 16 studies, with 3429 patients, including 731 referred for surgery. Carcinoembryonic antigen was better for clinically significant cysts (premalignant and malignant) with sensitivity = 0.58 (95% confidence interval [CI], 0.53–0.65), specificity = 0.9 (95% CI, 0.76–0.97), and area under the curve (AUC) = 0.69. Cytology performed better in malignant cysts, with sensitivity = 0.37 (95% CI, 0.27–0.48), specificity = 0.96 (95% CI, 0.93–0.98), and AUC = 0.78. Isolated, KRAS mutation failed the diagnosis of malignant and significant cysts, with sensitivities = 0.43 (95% CI, 0.34–0.43) and 0.46 (95% CI, 0.42–0.51), specificities = 0.62 (95% CI, 0.56–0.68) and 0.97 (95% CI, 0.92–0.99), and AUCs = 0.56 and 0.53, respectively. Carcinoembryonic antigen and cytology are more accurate than KRAS. Additional studies are lacking to recommend KRAS as a single diagnostic test.

The evolving role of EUS‐guided tissue acquisition

“…Cyst fluid molecular analysis to detect the KRAS mutation for predicting malignant and mucinous cysts is possible but not routinely available and the sensitivity is low. Faias et al in a meta‐analysis reported that KRAS mutation had sensitivities of 43% (95% CI 34%–43%) and 46% (95% CI 42%–51%) and specificities of 62% (95% CI 56%–68%) and 97% (95% CI 92%–99%) for the diagnosis of malignant and significant (malignant and mucinous) cysts, respectively 10 …”

Significance of KRAS mutation testing in biliary brushing cytology specimens: A 10‐year retrospective review

“…We observed a relatively low mutation rate (19%), moderate sensitivity (36%) but high specificity (92%) of KRAS mutation analysis in detecting malignant biliary strictures, which is consistent with previous reports 19,24,39 . In contrast, KRAS mutation testing in pancreatic FNA biopsy was reported to have overall sensitivity and specificity of 79% and 100%, respectively 34,38 . In pancreatic cystic fluid, the presence of KRAS mutation has been suggested as a highly specific test for mucinous cyst, with a reported sensitivity of 77% 33,35,36 .…”

“…33,35,36 These results suggest that KRAS mutational analysis has lower sensitivity and specificity in detecting malignancy in biliary tract brushing compared with that in pancreatic solid or cystic lesion FNAs. 24,33,34,38 The differences may be explained by a lower incidence of KRAS mutation rate in cholangiocarcinoma (5%) compared with pancreatic adenocarcinoma (66%), the inclusion of nonmalignant cytology cases in our study cohort, and the nature of overall limited cellularity in bile duct brushing specimens. However, given suboptimal sensitivity and diagnostic challenging in bile duct brushing cytology, KRAS mutation analysis is still a useful adjuvant molecular test for enhancing cytological diagnosis.…”

“…In pancreatic cystic fluid, the presence of KRAS mutation has been suggested as a highly specific test for mucinous cyst, with a reported sensitivity of 77% 33,35,36 . These results suggest that KRAS mutational analysis has lower sensitivity and specificity in detecting malignancy in biliary tract brushing compared with that in pancreatic solid or cystic lesion FNAs 24,33,34,38 . The differences may be explained by a lower incidence of KRAS mutation rate in cholangiocarcinoma (5%) compared with pancreatic adenocarcinoma (66%), the inclusion of nonmalignant cytology cases in our study cohort, and the nature of overall limited cellularity in bile duct brushing specimens.…”

“…KRAS mutation is a frequent oncogenic driver in many solid tumors, including pancreatic ductal adenocarcinoma and cholangiocarcinoma 20‐22 . KRAS mutation analysis has been used as an ancillary procedure for analysis of fine‐needle aspiration (FNA) of solid and cystic pancreatic masses, pancreas cystic lesions, and bile duct brushings 24,30‐34 . In pancreatic specimens, KRAS mutation has been identified in approximately 9% of benign conditions, including chronic pancreatitis, 10% of low‐grade dysplastic lesions, and 65% of invasive carcinomas 24,25,28,30,31‐38 .…”