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Cholangiocarcinoma and Gallbladder Cancer Studies / HER2/EGFR in Cancer Research · Journal article
Clinical Cancer Research · September 10, 2026
Early or partial results. Treat as a signal, not a conclusion.
This retrospective tissue microarray study of 65 resected biliary tract cancers documents the prevalence and heterogeneity of five ADC target antigens (TROP2, c-MET, Nectin-4, CLDN18.2, HER2) but finds no significant association between target expression and recurrence-free or overall survival. The work is exploratory and hypothesis-generating, establishing a descriptive baseline for target selection in BTC but stopping short of clinical utility evidence.
Retrospective cohort study with tissue microarray and targeted next-generation sequencing. 65 patients with resected biliary tract cancer (43% extrahepatic cholangiocarcinoma, 40% intrahepatic cholangiocarcinoma, 17% gallbladder cancer) with 18 paired metastatic sites available.. Intervention: Immunohistochemical staining for five ADC target antigens (CLDN18.2, c-MET, Nectin-4, TROP2, HER2); targeted next-generation sequencing (MSK-IMPACT) in a subset.. n = 65.
TROP2 expressed in 83% of tumors (H-score ≥200 in 26%); c-MET 75% (26%); Nectin-4 66% (35%); CLDN18.2 46% (7.7%); HER2 overexpression 3.1% Overall agreement between paired primary and metastatic samples ranged from 43% to 75%, with highest concordance for HER2 (75%; κ=0.29, 95% CI: −0.32 to 0.91) and TROP2 (71%) Lowest concordance observed for c-MET, CLDN18.2, and Nectin-4
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This study provides baseline prevalence data on ADC target expression in BTC but does not demonstrate that any target antigen predicts clinical benefit or prognosis. Clinicians should recognize substantial intertumoral and primary-metastatic heterogeneity in target expression and await prospective or biomarker-enriched ADC trials before making treatment decisions based on single-antigen status.
A single-center retrospective tissue microarray study with exploratory aims, no control group, and hypothesis-generating findings that establish target expression prevalence but lack sufficient power or design to establish clinical utility or practice-changing guidance.
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Quoted from the source exactly as published.
This study provides baseline prevalence data on ADC target expression in BTC but does not demonstrate that any target antigen predicts clinical benefit or prognosis. Clinicians should recognize substantial intertumoral and primary-metastatic heterogeneity in target expression and await prospective or biomarker-enriched ADC trials before making treatment decisions based on single-antigen status.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
BACKGROUND: Data on antibody-drug conjugates (ADCs) target expression prevalence, intertumoral heterogeneity, genomic concordance, and its effect on clinical outcomes is limited in biliary tract cancers (BTC). METHODS: Resected primary BTC specimens, and when available, matched metastatic samples were assembled into tissue microarrays and tested for CLDN18.2, c-MET, Nectin-4, TROP2, and HER2 expression by immunohistochemistry (IHC). A subset underwent targeted next-generation sequencing using MSK-IMPACT (NCT01775072). Exploratory associations of target expression with clinicopathologic parameters, genomic alterations, recurrence-free (RFS), and overall (OS) survival were evaluated. RESULTS: 65 patients with resected BTC and 18 paired metastatic sites were identified-43% extrahepatic cholangiocarcinoma, 40% intrahepatic cholangiocarcinoma, and 17% gallbladder cancer. All evaluated target antigens were expressed; percent positivity and H-score ≥200 were: TROP2 (83%, 26%), c-MET (75%, 26%), Nectin-4 (66%, 35%), and CLDN18.2 (46%, 7.7%). HER2 overexpression occurred in 3.1% of tumors. Overall agreement among paired primary and metastatic samples on calling either positive or negative ranged from 43% to 75% with the highest observed for HER2 [75%; κ=0.29 (95%CI: -0.32 to 0.91)] and TROP2 (71%; κ not available) and lowest for c-MET, CLDN18.2, and Nectin-4. Frequently altered genes included TP53 (36%), SMAD4 (27%), ELF3 (21%). We observed no significant association between target antigen expression with genomics, RFS, or OS. CONCLUSIONS: BTC displays frequent but heterogeneous expression of multiple ADC targets. These hypothesis generating findings suggest inherent complexity of target protein quantification, target threshold determination, and target sampling discordance. Future studies will be required to refine our understanding the utlitiy of ADCs in BTC.
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