{
  "abstract": "Background: Endometrial cancer (EC) is a heterogeneous disease comprising four molecular subtypes, one of which is mismatch repair-deficient (MMRd). Immunohistochemical (IHC) evaluation of MMR proteins typically reveals the loss of paired MMR protein expression. However, concurrent loss of all four MMR proteins, known as the null phenotype, is extremely rare and has been reported only in a few colorectal, gastric, and small bowel adenocarcinomas. The mechanisms underlying this unusual MMR IHC pattern remain unclear. Case Report: We describe a patient with EC showing concurrent loss of all four MMR proteins by IHC. Molecular analysis revealed hypermethylation of the MutL homolog 1 (MLH1) promoter and somatic mutations in MutS homolog 2 (MSH2). Germline genetic testing identified no pathogenic variants, suggesting that the MMR alterations were acquired somatically. To the best of our knowledge, this is the first reported case of EC with the null MMR phenotype. The coexistence of MLH1 promoter hypermethylation and MSH2 mutations suggests that multiple mechanisms of MMR disruption may occur within a single tumor. Conclusion: This case highlights the importance of recognizing unusual MMR IHC profiles in EC and performing molecular analyses to clarify the underlying genetic and epigenetic alterations. Although MMR deficiency can result from different mechanisms, including MLH1 promoter hypermethylation, Lynch syndrome, and somatic mutations, multiple mechanisms may coexist in an individual tumor. Accurate characterization of MMR deficiency is clinically relevant because MMR-deficient tumors are often microsatellite instability-high and may be eligible for immune checkpoint inhibitor therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gynecology and Obstetrics, Kagoshima University Graduate School of Medical and Dental Sciences, Japan; Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan",
    "Department of Surgical Pathology, Kagoshima University Hospital, Japan; Corresponding author at: Department of Surgical Pathology, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima 890-0075, Japan",
    "Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan; Center for Human Genome and Gene Analysis, Kagoshima University Hospital, Japan",
    "Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan",
    "Department of Gynecology and Obstetrics, Kagoshima University Graduate School of Medical and Dental Sciences, Japan",
    "Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan; Department of Surgical Pathology, Kagoshima University Hospital, Japan; Center for Human Genome and Gene Analysis, Kagoshima University Hospital, Japan"
  ],
  "article_type": "case report",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yuriko Higashi"
    },
    {
      "affs": [
        1
      ],
      "name": "Ikumi Kitazono"
    },
    {
      "affs": [
        2
      ],
      "name": "Toshiaki Akahane"
    },
    {
      "affs": [
        3
      ],
      "name": "Seiya Yokoyama"
    },
    {
      "affs": [
        4
      ],
      "name": "Shinichi Togami"
    },
    {
      "affs": [
        5
      ],
      "name": "Akihide Tanimoto"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/00z6edd3ng991.bib",
  "cited_by": 0,
  "doi": "10.1016/j.gore.2026.102237",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2352578926002171",
  "id": "00z6edd3ng991",
  "issns": [
    "2352-5789"
  ],
  "landing_url": "https://doi.org/10.1016/j.gore.2026.102237",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Survey Article"
    ],
    [
      "lcc",
      "RC254-282"
    ],
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      "lcc",
      "RG1-991"
    ],
    [
      "openalex",
      "2734|Genetic factors in colorectal cancer"
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  "openalex": "W7223381226",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "42964718",
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/00z6edd3ng991.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:47:23Z",
      "native_id": "bc6901f93ab144ab95883101a7de16ba",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.gore.2026.102237"
    },
    {
      "first_seen": "2026-11-03T12:22:29Z",
      "native_id": "PMC13721871",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.gore.2026.102237"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC254-282",
      "subfield": "oncology"
    },
    {
      "field": "medicine",
      "origin": "lcc:RG1-991",
      "subfield": "reproductive-child"
    }
  ],
  "title": "Complete loss of all mismatch repair protein expression in endometrioid carcinoma: A first case report of null phenotype induced by",
  "title_text": "Complete loss of all mismatch repair protein expression in endometrioid carcinoma: A first case report of null phenotype induced by",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:29Z",
  "url": "https://research.draconitic.com/paper/00z6edd3ng991",
  "venue": "Gynecologic Oncology Reports",
  "versions": []
}