The Expression of Human Epididymis Protein 4a (HE4) in the Normal Gastric Epithelia and Its Role in the Development of Intestinal Metaplasia and Gastric Cancer

Abstract

Background:  Biomarkers that allow early diagnosis of gastric carcinoma (GC) patients are limited. Human epididymal protein 4 (HE4) is a novel biomarker for epithelial ovarian and lung cancer. This study was designed to evaluate the role of HE4 in the development of intestinal metaplasia (IM) and gastric carcinoma. Methods: A total of 41 patients with a diagnosis of GC and 48 patients with a diagnosis of IM were enrolled. Gastric cancer samples were taken from patients who underwent gastric resection due to GC. For IM, biopsies obtained from patients who underwent endoscopic examination for non-tumoral reasons were used. Intestinal metaplasia adjacent to GC was also examined separately. For HE4 expression, immunohistochemistry was used and the results were compared to demographic, clinic, pathologic and prognostic parameters. Results: The patients were 38–90 years-old (mean: 65.6). Tumor localization were antrum in 37.8%, corpus in 27%, lesser curvature in 21.6%, greater curvature in 5.4%, and cardia in 8.1% of patients. Tumor sizes ranged between1-13 cm (mean 5.54). There were 37.8% well to moderately, and 62.2% poorly differentiated carcinoma. Pathological T evaluations were as follows: pT1=13.5%; pT2=8.1%; pT3=59.4%; pT4=18.9% patients. The expression of HE4 was seen in 50% of tumors. Among the tumor samples that harbor intestinal metaplasia, HE4 expression in metaplastic cells was seen in 61.1% of the cases. Diffuse type carcinoma had more HE4 expression than intestinal type cancers and there was an inverse correlation between depth of tumor invasion and the presence of HE4 (p=0.037). Conclusions: Human epididymal protein 4 was expressed in normal oxyntic glands and metaplastic cells as well as GC cells but not in the surface foveolar epithelium. It was expressed mostly in diffuse type carcinoma.  HE4 may be involved in personalized treatment in gastric cancer.