Development of a New Immunochemistry Method Using Antibodies of Proteins Related Bile Duct Cancer

Development of a New Immunochemistry Method Using Antibodies of Aminoacyl-tRNA Synthetases Group and Aminoacyl-transfer Ribonucleic Acid Synthetases-interacting Multifunctional protein2 Lacking Exon 2 in the Bile Duct Cancer Cell; Multicenter Study

The sensitivity of brushing cytology used to distinguish the cause of biliary strictures is low and clinical usefulness is not secured. The aim of this study was to develop a new differential staining method for cytology which is difficult to differentiate by the conventional staining method using biliary cancer related protein expressed only in bile duct cancer.

Hypothesis: The statistical significance of new staining method using aminoacyl-tRNA synthetases (ARSs) group in normal bile duct cells and the bile duct cancer cells collected by endoscopic retrograde pancreaticoduodenoscopy (ERCP) will be compared to prove the usefulness of the new staining method. Clinical study design: The bile duct cytology will be obtained by brushing cytology using ERCP in patients with biliary stenosis. The expression of ARSs in the brushing cytology will be evaluated by new staining method and compare with the results of conventional cytology staining method including Papanicolaou staining. Immunofluorescence or immunohistochemistry staining will be performed to differentiate the presence of the tumor. The sensitivity and specificity of the new staining method will be compared with the conventional staining method and its usefulness be confirmed.

The conventional staining method and new staining method will be performed in cytology specimens obtained from same patient.

This arm includes patients with bile duct stenosis. Endobiliary brushing cytology specimens will be obtained with endoscopic retrograde cholangiopancreatography (ERCP) of patients with bile duct stenosis. Cytology staining will be performed in the cytology specimens.

Two staining will be performed in cytology specimens obtained from same patient. The cytology specimen will be obtained through brushing cytology using endoscopic retrograde cholangiopancreatography conventional cytology staining method new cytology staining method using antibody of aminoacyl-tRNA synthetases

The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of new staining method will be compared with th conventional Pap staining of brushing cytology specimens.

Inclusion Criteria: Patients with biliary cancer confirmed by imaging (CT, MRI, positron emission tomography) Patients with bile duct cancer diagnosed using brushing cytology by endoscopic retrograde pancreaticoduodenoscopy Patients who underwent surgical treatment with biliary cancer Patients with bile duct stenosis Exclusion Criteria: Minors under the age of 19, vulnerable subjects such as illiteracy Necrotic specimens Samples with non-diagnostic cytology results and insufficient cells for further evaluation Samples classified as neoplastic (benign or other) Patient with cholangitis in the bile duct

We plan to share the following individual participant data with other researchers during study period. Study Protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF), Clinical Study Report (CSR), Analytic Code

Jang SI, Nahm JH, Kwon NH, Jeong S, Lee TH, Cho JH, Kwon CI, Kim DU, Kim JM, Cho HD, Lee HS, Kim S, Lee DK. Clinical utility of methionyl-tRNA synthetase 1 immunostaining in cytologic brushings of indeterminate biliary strictures: a multicenter prospective study. Gastrointest Endosc. 2021 Oct;94(4):733-741.e4. doi: 10.1016/j.gie.2021.04.026. Epub 2021 May 6.