John Cunningham virus T-antigen expression in anal carcinoma.
BACKGROUND
Anal carcinoma is thought to be driven by human papillomavirus (HPV) infection through interrupting function of cell regulatory proteins such as p53 and pRb. John Cunningham virus (JCV) expresses a T-antigen that causes malignant transformation through development of aneuploidy and interaction with some of the same regulatory proteins as HPV. JCV T-antigen is present in brain, gastric, and colon malignancies, but has not been evaluated in anal cancers. The authors examined a cohort of anal cancers for JCV T-antigen and correlated this with clinicopathologic data.


METHODS
Archived anal carcinomas were analyzed for JCV T-antigen expression. DNA from tumor and normal tissue was sequenced for JCV with viral copies determined by quantitative polymerase chain reaction and Southern blotting. HPV and microsatellite instability (MSI) status was correlated with JCV T-antigen expression.


RESULTS
Of 21 cases of anal cancer (mean age 49 years, 38% female), 12 (57%) were in human immunodeficiency virus (HIV)-positive individuals. All 21 cancers expressed JCV T-antigen, including 9 HPV-negative specimens. More JCV copies were present in cancer versus surrounding normal tissue (mean 32.54 copies/μg DNA vs 2.98 copies/μg DNA, P = .0267). There was no correlation between disease stage and viral copies, nor between viral copies and HIV-positive or -negative status (28.7 vs 36.34 copies/μg DNA, respectively, P = .7804). In subset analysis, no association was found between JCV T-antigen expression and HPV or MSI status.


CONCLUSIONS
Anal carcinomas uniformly express JCV T-antigen and contain more viral copies compared with surrounding normal tissue. JCV and its T-antigen oncogenic protein, presumably through interruption of cell regulatory proteins, may play a role in anal cancer pathogenesis.
Department of Surgery, University of California, San Diego, California; Moores Comprehensive Cancer Center, University of California, San Diego, California.
Sonia
S
Ramamoorthy
Bikash
B
Devaraj
Katsumi
K
Miyai
Linda
L
Luo
Yu-Tsueng
YT
Liu
C Richard
CR
Boland
Ajay
A
Goel
John M
JM
Carethers
D000328:Adult; D000368:Aged; D000957:Antigens, Viral, Tumor / Q000235:genetics* / Q000378:metabolism; D001005:Anus Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D027382:Polyomaviridae / Q000235:genetics*; D027601:Polyomavirus Infections / Q000821:virology; D014412:Tumor Virus Infections / Q000821:virology; D019562:Viral Load
D000957:Antigens, Viral, Tumor
John Cunningham virus; T-antigen; anal carcinoma; human immunodeficiency virus; human papilloma virus