title: Human epididymis protein 4 immunostaining of malignant ascites differentiates cancer of Müllerian origin from gastrointestinal cancer.
abstract: BACKGROUND
  An accurate diagnosis of cancer of Müllerian origin is required before the initiation of treatment. An overlap in clinical presentation and cytological, histological, or imaging studies with other nongynecological tumors does occur. Therefore, immunocytochemistry markers are used to determine tumor origin. Human epididymis protein 4 (HE4) is overexpressed in tissue of epithelial ovarian cancer (EOC). It has shown to be a sensitive and specific serum marker for EOC and to be of value for the differentiation between EOC and ovarian metastases of gastrointestinal origin. The objective of the current study was to evaluate HE4 immunocytochemistry in malignant ascites for differentiation between cancer of Müllerian origin, including EOC, and adenocarcinomas of the gastrointestinal tract.
  
  
  METHODS
  Cytological specimens of 115 different adenocarcinomas (45 EOCs, 46 cases of gastric cancer, and 24 cases of colorectal cancer) were stained for HE4, paired box 8 (PAX8), and other specific markers.
  
  
  RESULTS
  91% of the ascites samples from patients with EOC stained for both HE4 and PAX8. The 4 samples without HE4 staining were a clear cell carcinoma, a low-grade serous adenocarcinoma, an undifferentiated adenocarcinoma, and a neuroendocrine carcinoma. All high-grade serous adenocarcinomas (n = 37, 100%) stained with HE4, compared with 94% that stained positively for PAX8. In cases of gastric or colorectal cancer, 25% and 21% of cases, respectively, stained positive for HE4. No PAX8 staining was observed in colorectal or gastric adenocarcinomas.
  
  
  CONCLUSIONS
  HE4 staining in ascites is feasible and appears to have a high sensitivity for high-grade serous ovarian cancer. HE4 is a useful addition to the current panel of immunocytochemistry markers for the diagnosis of EOC and for differentiation with gastrointestinal adenocarcinomas. Cancer Cytopathol 2017;125:197-204. © 2016 American Cancer Society.
authors.affiliation: Department of Gynecology, Center for Gynecological Oncology, Amsterdam, the Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Stiekema
authors.affiliation: Department of Pathology, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
authors.forename: Koen K
authors.initials: KK
authors.lastname: Van de Vijver
authors.affiliation: Department of Gastroenterology, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Boot
authors.affiliation: Core Facility-Molecular Pathology and Biobank, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
authors.forename: Annegien
authors.initials: A
authors.lastname: Broeks
authors.affiliation: Department of Clinical Chemistry, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
authors.forename: Catharina M
authors.initials: CM
authors.lastname: Korse
authors.affiliation: Department of Gynecology, Center for Gynecological Oncology, Amsterdam, the Netherlands.
authors.forename: Willemien J
authors.initials: WJ
authors.lastname: van Driel
authors.affiliation: Department of Gynecology, Center for Gynecological Oncology, Amsterdam, the Netherlands.
authors.forename: Gemma G
authors.initials: GG
authors.lastname: Kenter
authors.affiliation: Department of Gynecology, Center for Gynecological Oncology, Amsterdam, the Netherlands.
authors.forename: Christianne A R
authors.initials: CA
authors.lastname: Lok
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D018278:Carcinoma, Neuroendocrine / Q000737:chemistry; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000556:secondary; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000473:pathology; D011506:Proteins / Q000032:analysis*; D013274:Stomach Neoplasms / Q000737:chemistry; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: epithelial ovarian cancer (EOC); gastrointestinal cancer; human epididymis protein 4 (HE4); immunostaining