{"doi":"10.1210/clinem/dgae672","title":"Detection of SEZ6, a Therapeutic Target, in Medullary Thyroid Carcinoma","abstract":"CONTEXT: Seizure-related 6 homolog (SEZ6) is a cDNA that is strongly associated with neuroendocrine differentiation. Recently, SEZ6 expression was found in a subset of small cell lung carcinoma (SCLC). Furthermore, ABBV-011, a novel antibody-drug conjugate targeting SEZ6 has been developed and is currently in a clinical trial for the treatment of SCLC and neuroendocrine neoplasms, including medullary thyroid carcinoma (MTC). OBJECTIVE: We herein present the first evidence that SEZ6 is highly expressed in MTC. METHODS: SEZ6 immuno-expression was studied in 78 MTCs and correlated with clinicopathologic characteristics, outcome, and molecular profile. RESULTS: SEZ6 was highly expressed in primary tumors, regional recurrence, and distant metastasis. Using 2 different SEZ6 antibody clones, SC17.14 and 14E5, SEZ6 immunopositivity was seen in 91% to 93% of primary MTCs, 100% of regional recurrence, and 75% to 83% of distant metastasis. High level of SEZ6 immuno-expression determined using H score was associated with male sex, advanced stage, and extrathyroidal thyroidal extension. There was no correlation between SEZ6 expression and outcome or RET/RAS mutation status in MTC. The frequency of SEZ6 positivity in MTC without RET/RAS mutations was 83%. CONCLUSION: SEZ6 may serve as a novel biomarker for MTCs. Although SEZ6 lacks any prognostic values in MTC, its positivity in 91% to 93% of MTCs, including MTCs without RET and RAS mutations, renders SEZ6-targeted antibody-drug conjugate therapy a promising targeted therapy for MTCs.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2024,"id":460137,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9654,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":616303,"name":"Marina K. Baine","orcid":"0000-0003-4939-6491","position":1,"is_corresponding":false},{"id":271415,"name":"Achim A. Jungbluth","orcid":"0000-0002-8949-2333","position":2,"is_corresponding":false},{"id":1258421,"name":"Anas Alabkaa","orcid":"0000-0001-5338-2944","position":3,"is_corresponding":false},{"id":1230752,"name":"Rene Serrette","orcid":null,"position":4,"is_corresponding":false},{"id":1230236,"name":"Dibisha Roy","orcid":"0009-0009-8612-1711","position":5,"is_corresponding":false},{"id":1288214,"name":"Carles M Rudin","orcid":null,"position":6,"is_corresponding":false},{"id":235764,"name":"Alan L. Ho","orcid":"0000-0002-6885-3742","position":7,"is_corresponding":false},{"id":255786,"name":"Eric J. Sherman","orcid":"0000-0002-4960-4783","position":8,"is_corresponding":false},{"id":90763,"name":"Snjezana Doğan","orcid":"0000-0002-4905-8946","position":9,"is_corresponding":false},{"id":267983,"name":"Ian Ganly","orcid":"0000-0001-7636-5426","position":10,"is_corresponding":false},{"id":15544,"name":"Natasha Rekhtman","orcid":"0000-0001-5801-3144","position":11,"is_corresponding":false},{"id":13486,"name":"Ronald Ghossein","orcid":"0000-0003-2802-8489","position":12,"is_corresponding":false},{"id":250488,"name":"Bin Xu","orcid":"0000-0003-4638-9835","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":null,"created_at":"2026-07-19T02:04:03.568045Z","pmid":"39324657","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}