{"type":"root","children":[{"type":"paragraph","children":[{"type":"text","value":"Human epididymis protein 4 (HE4), also known as WAP four-disulfide core domain protein 2, is a protein that in humans is encoded by the WFDC2 gene. This gene encodes a protein that is a member of the WFDC domain family. The WFDC domain, or WAP Signature motif, functions as a protease inhibitor in many family members. The encoded protein is a small secretory protein, which may be involved in sperm maturation. HE4 gene expression has been found the highest in normal human trachea and salivary gland, and to a lesser extent, lung, prostate, pituitary gland, thyroid, and kidney. HE4 immunoreactivity has also been found in normal glandular epithelium of the female genital tract and breast, the epididymis and vas deferens, respiratory epithelium, distal renal tubules, colonic mucosa, and salivary glands which is consistent with the HE4 gene expression."}]},{"type":"paragraph","children":[{"type":"text","value":"HE4 is a recognized biomarker in ovarian and endometrial cancer and over-expressed in pancreatic adenocarcinoma. In a series of 175 human adult tumors, gene expression was found to be the highest in ovarian serous carcinomas. However, adenocarcinomas of the lung, and occasional breast, transitional cell and pancreatic carcinomas had moderate or high levels of HE4 expression. IHC studies have shown that HE4 is significantly higher expressed in human pancreatic carcinoma tissues than in both normal and adjacent non-tumoral pancreatic tissues, and the staining intensity is inversely correlated with the clinical stage. HE4 is also highly expressed in early stage pancreatic adenocarcinoma."}]}]}