{
  "abstract": "Background\n\nSmall intestinal adenocarcinoma (SIA) is a rare gastrointestinal malignancy for which prognostic biomarkers remain poorly defined. Immunohistochemical markers cytokeratin 7 (CK7), cytokeratin 20 (CK20), and caudal-type homeobox transcription factor 2 (CDX2) are diagnostic markers that are prognostic in other intestinal cancers, but their prognostic significance in SIA has not been studied before.Patients and methods\n\nThis nationwide, retrospective, population-based cohort study used data from the Netherlands Cancer Registry and the Dutch pathology database. Patients diagnosed with primary SIA between 1999 and 2019 and with registered CK7, CK20, or CDX2 expression levels were included. Overall survival (OS) was analyzed using Kaplan-Meier curves and multivariable Cox regression models adjusted for age, sex, stage, tumor location, and treatment. The findings were validated in a detailed cohort of 128 SIA patients.Results\n\nOf 2697 patients diagnosed with SIA, expression data were available for 691 patients. CK7 positivity was associated with more proximal, advanced, and microsatellite stable tumors. CK7-negative, CK20-positive, and CDX2-positive tumors demonstrated significantly improved OS (all P ≤ 0.002). In multivariable analysis, lack of CK20 and CDX2 expression were independent predictors of poorer survival [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.02-1.83 and HR 1.51, 95% CI 1.06-2.17, respectively]. Combined expression profiles identified distinct prognostic subgroups, which were confirmed in the validation cohort.Conclusion\n\nCK20 and CDX2 expression are independent prognostic biomarkers in SIA, regardless of primary tumor location. Their assessment may improve risk stratification and refine disease classification, bridging diagnostic and prognostic utility in this rare cancer type.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam UMC and University of Amsterdam, Amsterdam, The Netherlands.",
    "Oncode Institute, Utrecht, The Netherlands.",
    "Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.",
    "Departments of Medical Oncology, Amsterdam UMC, Amsterdam, The Netherlands.",
    "Departments of Gastroenterology, Amsterdam UMC, Amsterdam, The Netherlands.",
    "Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.",
    "Departments of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.",
    "Departments of Surgery, Amsterdam UMC, Amsterdam, The Netherlands.",
    "Department of Pathology, OLVG, Amsterdam, The Netherlands.",
    "Netherlands Cancer Institute, Department of Gastrointestinal Oncology, Amsterdam, The Netherlands.",
    "Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands.",
    "Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.",
    "Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.",
    "Department of Internal Medicine, Meander Medical Center, Amersfoort, The Netherlands.",
    "Department of Internal Medicine, Flevo Hospital, Almere, The Netherlands."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
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        0,
        1,
        2,
        3
      ],
      "name": "P J M Schafrat"
    },
    {
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        0,
        1,
        2,
        4
      ],
      "name": "J D G Linssen"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "T R de Back"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "L E Nijman"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "M C S van der Heijden"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "N C T van Grieken"
    },
    {
      "affs": [
        5,
        7
      ],
      "name": "G Kazemier"
    },
    {
      "affs": [
        8
      ],
      "name": "P Drillenburg"
    },
    {
      "affs": [
        9
      ],
      "name": "M Chalabi"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "F N van Erning"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "I H J T de Hingh"
    },
    {
      "affs": [
        13
      ],
      "name": "R S A Goedegebuure"
    },
    {
      "affs": [
        5,
        14
      ],
      "name": "D W Sommeijer"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "A Farina Sarasqueta"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "L Vermeulen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8406kc4x9ecpw.bib",
  "cited_by": 0,
  "doi": "10.1016/j.esmogo.2026.100346",
  "fulltext_url": "https://europepmc.org/articles/PMC13712183",
  "id": "8406kc4x9ecpw",
  "issns": [
    "2949-8198"
  ],
  "landing_url": "https://europepmc.org/article/MED/42948310",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
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      "openalex",
      "2740|Gastric Cancer Management and Outcomes"
    ]
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  "openalex": "W7165171536",
  "pdf_url": "https://europepmc.org/articles/PMC13712183?pdf=render",
  "pmcid": "PMC13712183",
  "pmid": "42948310",
  "published": "2026-06-18",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/8406kc4x9ecpw.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:36Z",
      "native_id": "MED:42948310",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948310"
    },
    {
      "first_seen": "2026-10-31T12:22:49Z",
      "native_id": "PMC13712183",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.esmogo.2026.100346"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Gastric Cancer Management and Outcomes",
      "subfield": "general"
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  ],
  "title": "Prognostic significance of CK7, CK20, and CDX2 expression in small intestinal adenocarcinoma.",
  "title_text": "Prognostic significance of CK7, CK20, and CDX2 expression in small intestinal adenocarcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:49Z",
  "url": "https://research.draconitic.com/paper/8406kc4x9ecpw",
  "venue": "ESMO gastrointestinal oncology",
  "versions": []
}