Background and Aims: Identifying malignant biliary strictures using endobiliary brushing cytology specimens is important for treatment decision-making and prognosis prediction. The sensitivity of brushing cytology specimens based on Papanicolaou (Pap) staining is low, which hampers accurate diagnosis of indeterminate strictures. Here, we assessed the diagnostic value of immunohistochemical (IHC) and immunofluorescence (IF) staining for methionyl-tRNA synthetase 1 (MARS1). Methods: Endobiliary brushing cytology specimens were obtained during ERCP from 80 patients with an extrahepatic biliary stricture. Pap and MARS1 IF staining were performed on liquid-based cytology slides derived from these specimens. Sections of bile duct adenocarcinoma and normal bile duct tissue were obtained from 45 patients who underwent surgery for malignant biliary stricture, and MARS1 levels were evaluated by IHC staining. Results: MARS1 IF staining was applied to brushing cytology specimens, and the results showed strong signals in malignant biliary structures but not in the negative for malignancy specimens. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 70.4%, 96.2%, 97.4%, 56.8%, and 78.8%, respectively, for conventional Pap staining and 98.1%, 96.1%, 98.1%, 96.2%, and 97.5%, respectively, for MARS1 IF (P < .0001). When IHC staining was used, MARS1 was detected in 45 bile duct adenocarcinoma sections but not in 15 normal bile duct sections. Moreover, MARS1 mRNA and protein levels were significantly higher in bile duct adenocarcinoma sections according to polymerase chain reaction and Western blot, respectively. Conclusions: The high sensitivity and accuracy of MARS1 IF staining enabled detection of malignancy in patients with indeterminate biliary stricture. Further prospective studies are needed to validate our findings. (Clinical trial registration number: KCT 0003285.)
Bibliographical noteFunding Information:
We thank MID (Medical Illustration & Design), a part of the Medical Research Support Services of Yonsei University College of Medicine, for all artistic support related to this work. Research support for this study was provided by grants NRF-2014M3A6A4074817 (D. K. Lee), NRF-M3A6A4-2010-0029785 (S. Kim), and NRF2015M3A6A4065724 (N. H. Kwon) from the Global Frontier National Research Foundation, Ministry of Science and ICT (MSIT) of Korea; grants NRF-2017M3A9F7079378 (N. H. Kwon) and NRF-2018M3A9F7062524 (S. I. Jang) from the National Research Foundation, MSIT of Korea.
© 2020 American Society for Gastrointestinal Endoscopy
All Science Journal Classification (ASJC) codes
- Radiology Nuclear Medicine and imaging