Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas

Ryan L. O'Neal, Ki Taek Nam, Bonnie J. Lafleur, Brittney Barlow, Koji Nozaki, Hyuk Joon Lee, Woo Ho Kim, Han Kwang Yang, Chanjuan Shi, Anirban Maitra, Elizabeth Montgomery, M. Kay Washington, Wael El-Rifai, Ronny I. Drapkin, James R. Goldenring

Research output: Contribution to journalArticle

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Abstract

Upper gastrointestinal neoplasia in the esophagus, stomach, and pancreas is associated with the formation of preneoplastic 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/preneoplastic 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 the expression in metaplasias, the expression in cancer pathological subtypes, and the effects of expression on survival in patients with cancer. In patients with gastric cancer from Korea, HE4 was detected in 74% of intestinal and 90% of diffuse cancers, whereas in a gastric cancer cohort from Johns Hopkins, HE4 was detected in 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 the expression of HE4 in scattered endocrine cells within Barrett esophagus samples, but Barrett columnar metaplasias and HE4 were detected in only 2% of esophageal adenocarcinomas. Finally, in the pancreas, HE4 expression was not observed in pancreatic intraepithelial neoplasia lesions, but 46.8% of pancreatic adenocarcinomas expressed HE4. 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.

Original languageEnglish (US)
Pages (from-to)734-742
Number of pages9
JournalHuman Pathology
Volume44
Issue number5
DOIs
StatePublished - May 1 2013
Externally publishedYes

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Epididymis
Stomach
Adenocarcinoma
Proteins
Metaplasia
Stomach Neoplasms
Esophagus
Pancreas
Neoplasms
Barrett Esophagus
Survival
Endocrine Cells
Korea
Pancreatic Neoplasms
Carcinogenesis

Keywords

  • Adenocarcinoma
  • HE4
  • Metaplasia
  • WFDC2

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

O'Neal, R. L., Nam, K. T., Lafleur, B. J., Barlow, B., Nozaki, K., Lee, H. J., ... Goldenring, J. R. (2013). Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas. Human Pathology, 44(5), 734-742. https://doi.org/10.1016/j.humpath.2012.07.017

Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas. / O'Neal, Ryan L.; Nam, Ki Taek; Lafleur, Bonnie J.; Barlow, Brittney; Nozaki, Koji; Lee, Hyuk Joon; Kim, Woo Ho; Yang, Han Kwang; Shi, Chanjuan; Maitra, Anirban; Montgomery, Elizabeth; Washington, M. Kay; El-Rifai, Wael; Drapkin, Ronny I.; Goldenring, James R.

In: Human Pathology, Vol. 44, No. 5, 01.05.2013, p. 734-742.

Research output: Contribution to journalArticle

O'Neal, RL, Nam, KT, Lafleur, BJ, Barlow, B, Nozaki, K, Lee, HJ, Kim, WH, Yang, HK, Shi, C, Maitra, A, Montgomery, E, Washington, MK, El-Rifai, W, Drapkin, RI & Goldenring, JR 2013, 'Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas', Human Pathology, vol. 44, no. 5, pp. 734-742. https://doi.org/10.1016/j.humpath.2012.07.017
O'Neal, Ryan L. ; Nam, Ki Taek ; Lafleur, Bonnie J. ; Barlow, Brittney ; Nozaki, Koji ; Lee, Hyuk Joon ; Kim, Woo Ho ; Yang, Han Kwang ; Shi, Chanjuan ; Maitra, Anirban ; Montgomery, Elizabeth ; Washington, M. Kay ; El-Rifai, Wael ; Drapkin, Ronny I. ; Goldenring, James R. / Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas. In: Human Pathology. 2013 ; Vol. 44, No. 5. pp. 734-742.
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abstract = "Upper gastrointestinal neoplasia in the esophagus, stomach, and pancreas is associated with the formation of preneoplastic 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/preneoplastic 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 the expression in metaplasias, the expression in cancer pathological subtypes, and the effects of expression on survival in patients with cancer. In patients with gastric cancer from Korea, HE4 was detected in 74{\%} of intestinal and 90{\%} of diffuse cancers, whereas in a gastric cancer cohort from Johns Hopkins, HE4 was detected in 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 the expression of HE4 in scattered endocrine cells within Barrett esophagus samples, but Barrett columnar metaplasias and HE4 were detected in only 2{\%} of esophageal adenocarcinomas. Finally, in the pancreas, HE4 expression was not observed in pancreatic intraepithelial neoplasia lesions, but 46.8{\%} of pancreatic adenocarcinomas expressed HE4. 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.",
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AU - Nozaki, Koji

AU - Lee, Hyuk Joon

AU - Kim, Woo Ho

AU - Yang, Han Kwang

AU - Shi, Chanjuan

AU - Maitra, Anirban

AU - Montgomery, Elizabeth

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AU - El-Rifai, Wael

AU - Drapkin, Ronny I.

AU - Goldenring, James R.

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