Hepatocyte nuclear factor 4α as a sensitive marker for uterine endocervical adenocarcinomas and their precursors

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.