New staining method using methionyl-tRNA synthetase 1 antibody for brushing cytology of bile duct cancer

Sung Ill Jang; Nam Hoon Kwon; Beom Jin Lim; Ji Hae Nahm; Joon Seong Park; Chang Moo Kang; So Ra Park; Su Yun Lee Sd; Beom Sik Kang; Sunghoon Kim; Dong Ki Lee

doi:10.1016/j.gie.2019.12.017

New staining method using methionyl-tRNA synthetase 1 antibody for brushing cytology of bile duct cancer

Gastrointest Endosc. 2020 Aug;92(2):310-319.e6. doi: 10.1016/j.gie.2019.12.017. Epub 2019 Dec 24.

Authors

Affiliations

¹ Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
² Medicinal Bioconvergence Research Center, Seoul National University, Suwon, Gyeonggi-do, Korea.
³ Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
⁴ Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
⁵ Gangnam Severance Hospital and Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
⁶ School of Life Science and Biotechnology, Kyungpook National University, Daegu, Korea.
⁷ Medicinal Bioconvergence Research Center, Seoul National University, Suwon, Gyeonggi-do, Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, College of Pharmacy, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Gyeonggi-do, Korea.

PMID: 31874158
DOI: 10.1016/j.gie.2019.12.017

Abstract

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.).

MeSH terms

Bile Duct Neoplasms* / diagnosis
Bile Ducts
Bile Ducts, Intrahepatic
Cholangiopancreatography, Endoscopic Retrograde
Humans
Methionine-tRNA Ligase*
Prospective Studies
Sensitivity and Specificity
Staining and Labeling

Substances

Methionine-tRNA Ligase