title: Vitamin D receptor is highly expressed in precancerous lesions and esophageal adenocarcinoma with significant sex difference.
abstract: Bile acid reflux into the esophagus is important in the development of esophageal adenocarcinoma (EAC). Recently, vitamin D receptor (VDR) was recognized as a bile acid receptor as well as a vitamin receptor. Expression of VDR is reported to influence the development of various types of cancer, such as those of the breast, liver, and colon. However, little is known about the role of VDR in esophageal neoplasms. We investigated the clinicopathological role of VDR in esophageal tumors. We analyzed genomic DNA from 116 EACs for copy number aberrations. The VDR locus was amplified in 7% of EACs. Expression of the VDR protein was also detected by immunohistochemistry from tissue microarrays created from tissues of Barrett esophagus (BE), low-grade (LGD) and high-grade dysplasia (HGD), columnar cell metaplasia (CCM), squamous epithelium (SE), EAC, and esophageal squamous cell carcinoma (ESCC). The protein was highly expressed in 88% of CCM (58/66), 95% of BE (35/37), 100% of the 19 LGD, 94% of HGD (15/16), and 79% of EAC (86/109), but expression in SE and ESCC was rare. Female patients with EAC and CCM were significantly less likely to have high VDR expression than male patients. The overall survival rate was significantly different for patients with tumors exhibiting VDR amplification versus nonamplification. Our findings suggest that VDR plays a role in the early development of EAC through a bile acid ligand. The sex difference in VDR expression may help to explain why men have a high incidence of EAC.
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642. Electronic address: david_zhou@urmc.rochester.edu.
authors.forename: Zhongren
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Santhoshi
authors.initials: S
authors.lastname: Bandla
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Zakharov
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Peters
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Tony E
authors.initials: TE
authors.lastname: Godfrey
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612. Electronic address: jun_sun@rush.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D018167:Receptors, Calcitriol
keywords: Amplification; Barrett's esophagus; Esophageal adenocarcinoma; Overexpression; Sex difference; Vitamin D receptor