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

doi:10.1016/j.humpath.2012.07.017

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 journal › Article › peer-review

27 Scopus citations

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 language	English (US)
Pages (from-to)	734-742
Number of pages	9
Journal	Human pathology
Volume	44
Issue number	5
DOIs	https://doi.org/10.1016/j.humpath.2012.07.017
State	Published - May 2013
Externally published	Yes

Keywords

Adenocarcinoma
HE4
Metaplasia
WFDC2

ASJC Scopus subject areas

Pathology and Forensic Medicine

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10.1016/j.humpath.2012.07.017

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O'Neal, R. L., Nam, K. T., Lafleur, B. J., Barlow, B., Nozaki, K., Lee, H. J., Kim, W. H., Yang, H. K., Shi, C., Maitra, A., Montgomery, E., Washington, M. K., El Rifai, W., Drapkin, R. I., & 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

@article{884bf7a2a56a47cd99e0bd05d6a95907,

title = "Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas",

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.",

keywords = "Adenocarcinoma, HE4, Metaplasia, WFDC2",

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

note = "Funding Information: These studies were supported by grants from NIH RO1 DK071590 (J.R.G.), as well as ARRA Supplemental Funding from RO1 DK071590-S1, a Merit Review Award from the Department of Veterans Affairs, and funding from NIH U01 CA152990 (R.D.). This work was supported by core resources of the Vanderbilt Digestive Disease Center ( P30 DK058404 ), the Vanderbilt SPORE in Gastrointestinal Cancer Tissue Core ( P50 CA095103 ), the Vanderbilt Epithelial Biology Center, and the Vanderbilt-Ingram Cancer Center. ",

year = "2013",

month = may,

doi = "10.1016/j.humpath.2012.07.017",

language = "English (US)",

volume = "44",

pages = "734--742",

journal = "Human pathology",

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T1 - Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas

AU - O'Neal, Ryan L.

AU - Nam, Ki Taek

AU - Lafleur, Bonnie J.

AU - Barlow, Brittney

AU - Nozaki, Koji

AU - Lee, Hyuk Joon

AU - Kim, Woo Ho

AU - Yang, Han Kwang

AU - Shi, Chanjuan

AU - Maitra, Anirban

AU - Montgomery, Elizabeth

AU - Washington, M. Kay

AU - El Rifai, Wael

AU - Drapkin, Ronny I.

AU - Goldenring, James R.

N1 - Funding Information: These studies were supported by grants from NIH RO1 DK071590 (J.R.G.), as well as ARRA Supplemental Funding from RO1 DK071590-S1, a Merit Review Award from the Department of Veterans Affairs, and funding from NIH U01 CA152990 (R.D.). This work was supported by core resources of the Vanderbilt Digestive Disease Center ( P30 DK058404 ), the Vanderbilt SPORE in Gastrointestinal Cancer Tissue Core ( P50 CA095103 ), the Vanderbilt Epithelial Biology Center, and the Vanderbilt-Ingram Cancer Center.

PY - 2013/5

Y1 - 2013/5

N2 - 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.

AB - 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.

KW - Adenocarcinoma

KW - HE4

KW - Metaplasia

KW - WFDC2

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ER -

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

Abstract

Keywords

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