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

Abstract

Background/Purpose 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. Methods 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). Results 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. Conclusion 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.

Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis

“…iCCA, intrahepatic cholangiocarcinoma; p/dCCA, perihilar–distal cholangiocarcinoma; GBC, gallbladder cancer AVC, ampulla of Vater cancer. [ 12 , 13 , 23 , 24 , 29 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , …”

New Options for Systemic Therapies in Intrahepatic Cholangiocarcinoma (iCCA)

“…As of today, iCCA tumors are one of the cancers where personalized oncology is starting to play, or is already playing an important role. Targeted therapy Pemigatinib has been approved for 10–15% of patients with FGFR2 fusions/rearrangements and Ivosidenib is approved for a subgroup with the presence of IDH1 mutations [ 24 , 43 ]. Immunotherapy in combination with chemotherapy for the treatment of these cancers is also very promising in improving the survival of patients with inoperable disease, as evidenced by the results of the TOPAZ-1 trial with the addition of durvalumab to chemotherapy with gemcitabine and cisplatin and KEYNOTE-966-pembrolizumab with gemcitabine and cisplatin [ 15 , 17 ].…”

Novel Drug Candidate Prediction for Intrahepatic Cholangiocarcinoma via Hub Gene Network Analysis and Connectivity Mapping

“…To date, several targeted therapies have been approved for the treatment of advanced ICC. In particular, targeted therapy has been approved for the roughly 15-20% of patients with FGFR2 fusions/rearrangements/deletions, as well as a smaller subset of patients with IDH1 mutations or dMMR [39][40][41]. Unfortunately, only a small minority of patients with ICC have these specific targetable genetic perturbations and are eligible for these therapies.…”