Hepatocyte nuclear factor 4 alpha immunocytochemistry: A useful marker for detecting endocervical glandular lesions in alcohol-fixed smears

IF 3.2 3区医学 Q3 ONCOLOGY

Cancer Cytopathology Pub Date : 2025-07-21 DOI:10.1002/cncy.70034

Yuri Noda DDS, PhD, Kaori Sando CT, Masato Kita MD, PhD, Koji Tsuta MD, PhD

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Abstract

Background

Hepatocyte nuclear factor 4 alpha (HNF4α) contributes to tumorigenesis and cancer progression. This study evaluated the diagnostic potential of HNF4α for detecting endocervical glandular lesions (EGLs), including endocervical adenocarcinomas (ECAs), adenocarcinomas in situ (AIS), and lobular endocervical glandular hyperplasias (LEGH) using alcohol-fixed cytological smears.

Methods

HNF4α expression was immunocytochemically assessed in alcohol-fixed smears and paired formalin-fixed paraffin-embedded tissue specimens obtained from 14 patients with histologically confirmed EGLs: eight papillomavirus-associated (HPVA) ECAs, one non-NHPVA ECA, two HPVA AIS, and three patients with LEGHs. Three cases of squamous cell carcinomas (SCCs) and two cases of non-neoplastic lesions were also analyzed as non-EGL controls. HNF4α positivity was defined as nuclear staining in one or more cell(s)/slide, regardless of intensity.

Results

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 HNF4α expression was observed in atypical glands in both smears and tissue specimens, whereas non-neoplastic glands and non-neoplastic/neoplastic squamous epithelium were HNF4α-negative. HNF4α expression showed 73.7% concordance between tissue and smear samples. Notably, HNF4α immunocytochemistry demonstrated 100% sensitivity and specificity for detecting EGLs, outperforming cytomorphological or immunohistochemical diagnosis (sensitivity, 71.4%; specificity, 100%).

Conclusions

HNF4α is a reliable diagnostic marker when using alcohol-fixed smears, showing enhanced accuracy for EGLs detection regardless of human papillomavirus status. Immunocytochemical analysis of HNF4α in cervical smears can be used for EGL detection and early diagnosis of cervical cancer.

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肝细胞核因子4免疫细胞化学：一种检测宫颈内腺体病变的有用标记物

肝细胞核因子4α (HNF4α)参与肿瘤发生和癌症进展。本研究评估了HNF4α在检测宫颈内腺病变（EGLs）中的诊断潜力，包括宫颈内腺癌（ECAs）、原位腺癌（AIS）和小叶宫颈内腺增生（LEGH）。方法采用免疫细胞化学方法对14例组织学证实的EGLs患者（8例乳头瘤病毒相关（HPVA） ECAs， 1例非nhpva ECAs， 2例HPVA AIS和3例LEGHs）的酒精固定涂片和配对的福尔马林固定石蜡包埋组织标本进行HNF4α表达检测。3例鳞状细胞癌（SCCs）和2例非肿瘤性病变也作为非egl对照进行分析。HNF4α阳性定义为细胞核染色在一个或多个细胞(s)/片，无论强度。结果组织学确诊的EGL病例细胞学诊断为腺癌4例，非典型腺细胞8例，误分意义不明的非典型鳞状细胞1例，误分SCC 1例，敏感性为85.7%，特异性为100%。在非典型腺体和组织标本中，HNF4α表达强烈且弥漫性，而非肿瘤性腺体和非肿瘤性/肿瘤性鳞状上皮中HNF4α表达阴性。HNF4α在组织和涂片样品中的表达一致性为73.7%。值得注意的是，HNF4α免疫细胞化学检测egl的灵敏度和特异性为100%，优于细胞形态学或免疫组织化学诊断(灵敏度为71.4%；特异性,100%)。结论HNF4α是一种可靠的酒精固定涂片诊断标志物，无论人乳头瘤病毒状态如何，其检测egl的准确性都有所提高。宫颈涂片HNF4α免疫细胞化学分析可用于EGL检测和宫颈癌早期诊断。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cytopathology 医学-病理学

CiteScore

7.00

自引率

17.60%

发文量

130

审稿时长

1 months

期刊介绍： Cancer Cytopathology provides a unique forum for interaction and dissemination of original research and educational information relevant to the practice of cytopathology and its related oncologic disciplines. The journal strives to have a positive effect on cancer prevention, early detection, diagnosis, and cure by the publication of high-quality content. The mission of Cancer Cytopathology is to present and inform readers of new applications, technological advances, cutting-edge research, novel applications of molecular techniques, and relevant review articles related to cytopathology.