{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:53:47Z","timestamp":1760316827932,"version":"build-2065373602"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatocyte nuclear factor 4 alpha (HNF4\u03b1) contributes to tumorigenesis and cancer progression. This study evaluated the diagnostic potential of HNF4\u03b1 for detecting endocervical glandular lesions (EGLs), including endocervical adenocarcinomas (ECAs), adenocarcinomas in situ (AIS), and lobular endocervical glandular hyperplasias (LEGH) using alcohol\u2010fixed cytological smears.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HNF4\u03b1 expression was immunocytochemically assessed in alcohol\u2010fixed smears and paired formalin\u2010fixed paraffin\u2010embedded tissue specimens obtained from 14 patients with histologically confirmed EGLs: eight papillomavirus\u2010associated (HPVA) ECAs, one non\u2010NHPVA ECA, two HPVA AIS, and three patients with LEGHs. Three cases of squamous cell carcinomas (SCCs) and two cases of non\u2010neoplastic lesions were also analyzed as non\u2010EGL controls. HNF4\u03b1 positivity was defined as nuclear staining in one or more cell(s)\/slide, regardless of intensity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Histologically confirmed EGL cases were cytologically diagnosed as four adenocarcinomas, eight atypical glandular cells, one misclassified atypical squamous cells of undetermined significance, and one misclassified SCC, with a sensitivity of 85.7% and specificity of 100%. Strong and diffuse nuclear HNF4\u03b1 expression was observed in atypical glands in both smears and tissue specimens, whereas non\u2010neoplastic glands and non\u2010neoplastic\/neoplastic squamous epithelium were HNF4\u03b1\u2010negative. HNF4\u03b1 expression showed 73.7% concordance between tissue and smear samples. Notably, HNF4\u03b1 immunocytochemistry demonstrated 100% sensitivity and specificity for detecting EGLs, outperforming cytomorphological or immunohistochemical diagnosis (sensitivity, 71.4%; specificity, 100%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HNF4\u03b1 is a reliable diagnostic marker when using alcohol\u2010fixed smears, showing enhanced accuracy for EGLs detection regardless of human papillomavirus status. Immunocytochemical analysis of HNF4\u03b1 in cervical smears can be used for EGL detection and early diagnosis of cervical cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.70034","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T14:43:30Z","timestamp":1753109010000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatocyte nuclear factor 4 alpha immunocytochemistry: A useful marker for detecting endocervical glandular lesions in alcohol\u2010fixed smears"],"prefix":"10.1002","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8041-0074","authenticated-orcid":false,"given":"Yuri","family":"Noda","sequence":"first","affiliation":[{"name":"Department of Pathology Kansai Medical University  Osaka Japan"},{"name":"Department of Pathology and Laboratory Medicine Kansai Medical University Hospital  Osaka 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