{
  "abstract": "INTRODUCTION: Multi-omic studies have identified three molecular separated pulmonary carcinoid (PC) subgroups (A1, A2, B) with distinctive mRNA expression profiles (e.g., orthopedia homeobox protein [OTP], achaete-scute homolog [ASCL1], and hepatocyte nuclear factor 1 homeobox A [HNF1A]). We aimed to establish an immunohistochemical (IHC) biomarker panel that enables subgroup identification, and assessment of its potential clinical relevance. METHODS: All patients with resected pulmonary carcinoids (2003-2012) were identified from the Dutch Cancer/Pathology Registry, and tumors were revised. The IHC expression of OTP, ASCL1, and HNF1A was scored in a blinded fashion in a mRNA-profiled (n = 5 per subgroup) and national carcinoid cohort (N = 478). The expression of potential therapeutic targets (somatostatin receptor type 2a [SSTR2A] and delta-like canonical Notch ligand 3 [DLL3]) was assessed. Immunohistochemistry was assessed using H-scoring. RESULTS: ). In 12% of PCs, no distinct classification could be provided. Patients with A1 were enriched for older age (83% > 50 y), female individuals (83%), and peripheral location (55%) with low SSTR2A (median = 10) and high DLL3 (median = 52) expression. A2 included younger patients (34% < 40 y) and endobronchial/central (87%) tumors with high SSTR2A (median = 160), but low DLL3 (median 0) expression. Group B included more male individuals (59%) and recurrence was more frequent (19%) than in groups A1 (8%) and A2 (6%). Neuroendocrine cell hyperplasia was enriched in A1 (25%) compared with A2 (3%) and B (0%). CONCLUSIONS: An OTP, ASCL1, and HNF1A IHC panel enables the identification of molecular-defined pulmonary carcinoid subgroups with distinct clinical phenotypes and diverging therapeutic vulnerabilities that require further prospective evaluation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "name": "Daphne J. G. Leunissen"
    },
    {
      "name": "Laura Moonen"
    },
    {
      "name": "Jan H. von Der Thüsen"
    },
    {
      "name": "Michael A. Den Bakker"
    },
    {
      "name": "Lisa M. Hillen"
    },
    {
      "name": "Tijmen J. J. Van Weert"
    },
    {
      "name": "Axel Zur Hausen"
    },
    {
      "name": "Thierry P. P. van Den Bosch"
    },
    {
      "name": "Lisa M. V. Lap"
    },
    {
      "name": "Ronald A. Damhuis"
    },
    {
      "name": "Niki L. Reynaert"
    },
    {
      "name": "Esther C. van Den Broek"
    },
    {
      "name": "Lynnette Fernandez-Cuesta"
    },
    {
      "name": "Matthieu Foll"
    },
    {
      "name": "Nicolas Alcala"
    },
    {
      "name": "Alexandra Sexton-Oates"
    },
    {
      "name": "Anne-Marie C. Dingemans"
    },
    {
      "name": "Ernst-Jan M. Speel"
    },
    {
      "name": "Jules L. Derks"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/248w0fcd03xw1.bib",
  "cited_by": 29,
  "doi": "10.1016/j.jtho.2024.11.018",
  "fulltext_url": null,
  "id": "248w0fcd03xw1",
  "issns": [
    "1556-0864",
    "1556-1380"
  ],
  "landing_url": "https://hal.science/hal-05842060v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.can"
    ],
    [
      "openalex",
      "2713|Neuroendocrine Tumor Research Advances"
    ]
  ],
  "openalex": "W4404625225",
  "pdf_url": "https://www.jto.org/article/S1556-0864(24)02481-X/pdf",
  "pmcid": null,
  "pmid": "39581377",
  "published": "2026-10-28",
  "publisher": "Lippincott, Williams & Wilkins",
  "ris": "https://research.draconitic.com/paper/248w0fcd03xw1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "hal-05842060",
      "source": "hal",
      "url": "https://hal.science/hal-05842060v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:0.sdv",
      "subfield": "general"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.can",
      "subfield": "oncology"
    }
  ],
  "title": "Identification of Defined Molecular Subgroups on the Basis of Immunohistochemical Analyses and Potential Therapeutic Vulnerabilities of Pulmonary Carcinoids",
  "title_text": "Identification of Defined Molecular Subgroups on the Basis of Immunohistochemical Analyses and Potential Therapeutic Vulnerabilities of Pulmonary Carcinoids",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/248w0fcd03xw1",
  "venue": "Journal of Thoracic Oncology",
  "versions": []
}