Detection of JC virus DNA sequences and expression of viral T antigen and agnoprotein in esophageal carcinoma.
BACKGROUND
The human polyomavirus JC virus (JCV) causes progressive multifocal leukoencephalopathy. Subclinical infection with JCV occurs in 85-90% of the population worldwide. The virus usually remains latent but can reactivate under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy. JCV is oncogenic in experimental animals and is associated with human brain tumors. JCV is found in normal mucosa of the gastrointestinal tract, and some colon carcinomas express the oncogenic JCV T-antigen protein. The objective of this study was to examine the presence of JCV DNA sequences and JCV protein expression in normal and malignant human esophageal tissues.


METHODS
The authors examined the presence of JCV DNA sequences and protein expression in normal and malignant human esophageal tissues. Seventy well characterized biopsy specimens from patients with a spectrum of esophageal disorders were studied by immunohistochemistry, and 18 specimens were analyzed further by polymerase chain reaction amplification.


RESULTS
JC viral DNA was isolated from 11 of 13 normal esophageal biopsy specimens (85%) and from 5 of 5 esophageal carcinomas (100%). Using immunohistochemistry, JCV T antigen was detected in 10 of 19 carcinomas (53%), agnoprotein was detected in 8 carcinomas (42%), p53 tumor suppressor was detected in 11 carcinomas (58%), and beta-catenin was detected in 4 carcinomas (21%). Zero of 51 normal, benign, and premalignant esophageal samples expressed viral proteins. Laser-capture microdissection verified the presence and specificity of JCV DNA sequences. beta-Catenin and p53 were colocalized with JCV T-antigen in the nuclei of neoplastic cells.


CONCLUSIONS
The results provide evidence for infection of gastrointestinal tract cells by JCV and suggest a potential role of JCV in the development of upper digestive tract carcinomas.
Del Valle
Luis
L
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, USA.
White
Martyn K
MK
Enam
Sahnila
S
Piña Oviedo
Sergio
S
Bromer
Matthew Q
MQ
Thomas
Rebecca M
RM
Parkman
Henry P
HP
Khalili
Kamel
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000957:Antigens, Viral, Tumor / Q000032:analysis*; D004279:DNA, Viral / Q000302:isolation & purification; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000276:immunology / Q000821:virology*; D004947:Esophagus / Q000821:virology; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000235:genetics / Q000302:isolation & purification*; D007834:Lasers; D008297:Male; D042282:Microdissection / Q000379:methods; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000150:complications / Q000175:diagnosis*; D014412:Tumor Virus Infections / Q000150:complications / Q000175:diagnosis*; D014764:Viral Proteins / Q000032:analysis*; D054334:Viral Regulatory and Accessory Proteins; D000086082:Viroporin Proteins
D000957:Antigens, Viral, Tumor; D004279:DNA, Viral; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins