Clinical utility of methionyl-tRNA synthetase 1 immunostaining in cytologic brushings of indeterminate biliary strictures: a multicenter prospective study

Abstract Background and Aims Endobiliary brushings are routinely used in the diagnosis, treatment, and prognostication of biliary strictures. However, standard Papanicolaou (Pap) staining has a low sensitivity in this setting, and the accuracy of brush cytology has not been established for indeterminate strictures. We therefore evaluated the diagnostic merit of methionyl-tRNA synthetase 1 (MARS1) immunofluorescence (IF) staining in such cytologic specimens. Methods During endoscopic retrograde cholangiopancreatography, endobiliary brushings were obtained from patients with extrahepatic biliary strictures prospectively enrolled at 6 tertiary hospitals. Using liquid-based cytologic preparations of these samples, we performed Pap and MARS1 IF staining. Results In total, 240 patients were eligible; of these, we compared the Pap and MARS1 IF staining results of 218 (malignant, 157; benign, 61). By conventional Pap staining, the diagnoses were distributed as follows: malignant, 55 suspicious of malignancy, 60 atypical, 45; and negative for malignancy, 58. MARS1 IF staining was strongly positive in malignant biliary stricture, but not so in specimens negative for malignancy. The diagnostic parameters (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of the MARS1 IF (93.6%, 96.7%, 98.7%, 85.5%, and 94.5%, respectively) and conventional Pap (73.2%, 100%, 100%, 59.2%, and 80.7%, respectively) staining methods differed significantly (p Conclusions The high sensitivity and accuracy of MARS1 IF staining enabled detection of malignancy in patients with biliary strictures. Further prospective studies are needed to validate our findings (NCT03708445 at ClinicalTrials.gov).