Prediction of mismatch repair deficient biliary tract cancer: Role of morphological features and host immune response detected by routine hematoxylin-eosin staining.

Abstract

The objective of this study was to determine the frequency and predictors of biliary tract cancer (BTC) with deficient DNA mismatch repair (dMMR) in Japan. Immunostaining and microsatellite instability analysis were performed for mismatch repair-related proteins in tissue specimens from 662 patients who underwent surgery for BTC between 2001 and 2017 to identify dMMR-BTC. We compared dMMR-BTC and proficient MMR (pMMR)-BTC based on patient demographics, pathological features, and host immune responses characterized by the percentage of stromal tumor infiltrating lymphocytes (sTIL percentage) and tertiary lymphoid structures (TLS). The incidence of dMMR-BTC was 2.3%. Significant predictors of dMMR-BTC were its primary lesion being intrahepatic cholangiocarcinoma (odds ratio [OR] 6.34, P=.004), presence of signet ring cell component (OR 35.62, P<.001), sTIL percentage ≥40% (OR 3.43, P=.038), and presence of TLS (OR 22.22, P<.001). The sensitivity, specificity, and negative likelihood ratio for any one or more of these four variables to be positive were 93.3%, 57.8%, and 0.12, respectively. Evaluation of histopathological findings and host immune response based on conventional histochemical staining is useful for efficient and inexpensive diagnostic screening of dMMR-BTC patients.