Noda Yuri, Tokuyama Yoko, Sumita Wataru, Kita Masato, Tsuta Koji
Department of Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka, 573-1010, Japan.
Department of Obstetrics and Gynecology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka, 573-1010, Japan.
Hum Pathol. 2025 Jan;155:105714. doi: 10.1016/j.humpath.2025.105714. Epub 2025 Jan 10.
Hepatocyte nuclear factor (HNF)-4α is a marker of gastrointestinal tumor differentiation; however, its expression in endocervical tumors remains unclear.
We aimed to assess the utility of HNF4α expression as a marker for endocervical adenocarcinomas (ECAs) and adenocarcinoma in situs (AISs), and to establish a minimal panel for distinguishing them from nonneoplastic endocervical glandular lesions and metastases.
HNF4α expression was analyzed immunohistochemically (positive, H-score ≥10) in 323 tissue samples: 57 endocervical neoplasms including 35 glandular neoplasms and 22 squamous neoplasms, 144 nonneoplastic endocervical lesions, and 122 tumors from other organs. The panel for distinguishing endocervical glandular neoplasms from nonneoplastic glands and from metastases comprised HNF4α, p16, CDX2, and SATB2; staining was assessed.
HNF4α was expressed significantly in ECAs and AISs, both HPV-independent and -associated types, but not in nonneoplastic glandular and squamous lesions (p < 0.05). The immunohistochemical detection sensitivity and specificity for endocervical ECA and AIS were 77% and 95%, respectively. For AIS alone, these were 79% and 94%, and for ECA alone, 75% and 94%, respectively. Either HNF4α(+) or p16(+) or double positive identified endocervical gland and squamous neoplasms (sensitivity, 96%; specificity, 76%). HNF4α(+) and SATB2(-) and CDX2(-) profiles suggested ECAs (sensitivity, 69%; specificity, 88%). HNF4α(+) and SATB2(+) or CDX2(+) profiles suggested adenocarcinomas of the gastrointestinal or genital tract (sensitivity, 81%; specificity, 88%).
HNF4α is a promising marker for detecting both HPV-independent and -associated ECAs and AIS with high accuracy. Its combination with p16, CDX2, and SATB2 has potential use in diagnostic panels.
肝细胞核因子（HNF）-4α是胃肠道肿瘤分化的标志物；然而，其在宫颈内膜肿瘤中的表达仍不清楚。
我们旨在评估HNF4α表达作为宫颈内膜腺癌（ECA）和原位腺癌（AIS）标志物的效用，并建立一个最小化的检测组合，以将它们与非肿瘤性宫颈内膜腺性病变和转移瘤区分开来。
采用免疫组织化学方法分析323份组织样本中HNF4α的表达情况（阳性：H评分≥10），这些样本包括57例宫颈内膜肿瘤，其中35例为腺性肿瘤，22例为鳞状肿瘤；144例非肿瘤性宫颈内膜病变；以及122例来自其他器官的肿瘤。用于区分宫颈内膜腺性肿瘤与非肿瘤性腺体及转移瘤的检测组合包括HNF4α、p16、CDX2和SATB2；对染色情况进行评估。
HNF4α在ECA和AIS中均有显著表达，包括HPV非相关型和相关型，但在非肿瘤性腺性和鳞状病变中无表达（p<0.05）。宫颈内膜ECA和AIS的免疫组织化学检测敏感性和特异性分别为77%和95%。单独针对AIS，分别为79%和94%；单独针对ECA，分别为75%和94%。HNF4α(+)或p16(+)或双阳性可识别宫颈内膜腺性和鳞状肿瘤（敏感性96%；特异性76%）。HNF4α(+)且SATB2(-)和CDX2(-)的特征提示为ECA（敏感性69%；特异性88%）。HNF4α(+)且SATB2(+)或CDX2(+)的特征提示为胃肠道或生殖道腺癌（敏感性81%；特异性88%）。
HNF4α是一种很有前景的标志物，可高精度检测HPV非相关型和相关型ECA及AIS。它与p16、CDX2和SATB2联合使用在诊断检测组合中有潜在应用价值。
