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Updated: Aug 9, 2026
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Extraction of Histones from Clinical Specimens for Epigenetic Profiling by Mass Spectrometry
Published on: November 21, 2025
Comprehensive analysis of HE4 expression in normal and malignant human tissues
Mary T Galgano1, Garret M Hampton, Henry F Frierson
1Department of Pathology, Robert E. Fechner Laboratory of Surgical Pathology, University of Virginia Medical Center, Charlottesville, VA 22908, USA.
Summary
The HE4 (WFDC2) gene is upregulated in ovarian cancer. This study maps HE4 gene and protein expression across normal and cancerous adult tissues, aiding diagnostic and therapeutic applications.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- The HE4 (WFDC2) gene, encoding a protein involved in natural immunity, shows consistent upregulation in ovarian carcinomas.
- Detailed examination of HE4 expression in normal and malignant adult tissues is lacking.
- Understanding HE4 expression patterns is crucial for its potential as a diagnostic biomarker and therapeutic target.
Purpose of the Study:
- To comprehensively analyze the expression of the HE4 gene and protein in a wide range of normal and malignant adult tissues.
- To correlate HE4 expression with specific cancer types and normal tissue distribution.
- To evaluate the utility of HE4 expression data in histopathologic diagnosis and future research.
Main Methods:
- Oligonucleotide microarrays were used to assess HE4 gene expression.
- Tissue microarrays and full tissue sections were employed for HE4 protein (immunoreactivity) analysis.
- A large series of normal adult tissues (n=?) and neoplastic tissues (n=448) were examined.
Main Results:
- HE4 gene expression was highest in normal trachea and salivary glands, with notable levels in lung, prostate, pituitary, thyroid, and kidney.
- Ovarian serous carcinomas exhibited the highest HE4 gene expression among 175 human adult tumors.
- HE4 protein was detected in normal glandular epithelium (female genital tract, breast), epididymis, respiratory tract, renal tubules, colon, and salivary glands.
- Consistent HE4 positivity was observed in ovarian carcinoma, with additional expression in pulmonary, endometrial, breast adenocarcinomas, mesotheliomas, and some gastrointestinal, renal, and transitional cell carcinomas.
Conclusions:
- HE4 exhibits a distinct expression pattern in normal adult tissues, with significant presence in glandular and respiratory epithelia.
- HE4 is highly expressed in ovarian carcinomas and also found in various other adenocarcinomas and mesotheliomas.
- Knowledge of HE4 expression profiles is valuable for histopathologic diagnosis and informs its potential as a serological biomarker or gene therapy target.
