Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas.
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.
Nashville VA Medical Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Ryan L
RL
O'Neal
Ki Taek
KT
Nam
Bonnie J
BJ
LaFleur
Brittney
B
Barlow
Koji
K
Nozaki
Hyuk-Joon
HJ
Lee
Woo Ho
WH
Kim
Han-Kwang
HK
Yang
Chanjuan
C
Shi
Anirban
A
Maitra
Elizabeth
E
Montgomery
M Kay
MK
Washington
Wael
W
El Rifai
Ronny I
RI
Drapkin
James R
JR
Goldenring
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology; D004947:Esophagus / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008679:Metaplasia / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015854:Up-Regulation; D000081102:WAP Four-Disulfide Core Domain Protein 2
D014408:Biomarkers, Tumor; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human