Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas
Ryan L. O’Neal ; Ki Taek Nam ; James R. Goldenring ; Ronny I. Drapkin ; Wael El Rifai ; M. Kay Washington ; Elizabeth Montgomery ; Anirban Maitra ; Chanjuan Shi ; Han-Kwang Yang ; Woo Ho Kim ; Hyuk-Joon Lee ; Koji Nozaki ; Brittney Barlow ; Bonnie J. LaFleur
Human Pathology, Vol.44(5) : 734~742, 2013
Upper gastrointestinal neoplasia in the esophagus, stomach and pancreas is associated with the formation of pre-neoplastic metaplasias. We have previously reported the up-regulation of Human epididymis protein 4 (HE4) in all metaplasias in the stomach of humans and mice. We have now sought to evaluate the expression of HE4 in metaplasias/pre-neoplastic precursors and cancers of the human stomach, pancreas and esophagus. Tissue microarrays for gastric cancers, pancreatic cancers and esophageal adenocarcinoma were stained with antibodies against HE4. Immunostaining was quantified by digital imaging and the results were evaluated to assess expression in metaplasias, expression in cancer pathological subtypes and the effects of expression on survival in cancer patients. In gastric cancer patients from Korea, HE4 was detected in 74% of intestinal and 90% of diffuse cancers, while in a gastric cancer cohort from Johns Hopkins HE4 was detected 74% of intestinal type and 92% of diffuse cancers. Nevertheless, in both cohorts there was no impact of HE4 expression on overall survival. In the esophagus, we observed expression of HE4 in scattered endocrine cells within Barrett’s esophagus samples, but Barrett’s columnar metaplasias and HE4 was detected in only 2% of esophageal adenocarcinomas. Finally, in the pancreas, HE4 expression was not observed in pancreatic intraepithelial neoplasia (PanIN) lesions, but 46.8% of pancreatic adenocarcinomas expressed HE4 expression. Still, we did not observe any influence of HE4 expression on survival. The results suggest that HE4 is up-regulated during gastric and pancreatic carcinogenesis.