Antibodies to merkel cell polyomavirus T antigen oncoproteins reflect tumor burden in merkel cell carcinoma patients.
Merkel cell polyomavirus (MCPyV) is a common infectious agent that is likely involved in the etiology of most Merkel cell carcinomas (MCC). Serum antibodies recognizing the MCPyV capsid protein VP1 are detectable at high titer in nearly all MCC patients and remain stable over time. Although antibodies to the viral capsid indicate prior MCPyV infection, they provide limited clinical insight into MCC because they are also detected in more than half of the general population. We investigated whether antibodies recognizing MCPyV large and small tumor-associated antigens (T-Ag) would be more specifically associated with MCC. Among 530 population control subjects, these antibodies were present in only 0.9% and were of low titer. In contrast, among 205 MCC cases, 40.5% had serum IgG antibodies that recognize a portion of T-Ag shared between small and large T-Ags. Among cases, titers of T-Ag antibodies fell rapidly (∼8-fold per year) in patients whose cancer did not recur, whereas they rose rapidly in those with progressive disease. Importantly, in several patients who developed metastases, the rise in T-Ag titer preceded clinical detection of disease spread. These results suggest that antibodies recognizing T-Ag are relatively specifically associated with MCC, do not effectively protect against disease progression, and may serve as a clinically useful indicator of disease status.
Division of Human Biology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington 98109, USA.
Kelly G
KG
Paulson
Joseph J
JJ
Carter
Lisa G
LG
Johnson
Kevin W
KW
Cahill
Jayasri G
JG
Iyer
David
D
Schrama
Juergen C
JC
Becker
Margaret M
MM
Madeleine
Paul
P
Nghiem
Denise A
DA
Galloway
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology*; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology*; D015266:Carcinoma, Merkel Cell / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D018862:Merkel Cells / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D011120:Polyomavirus / Q000235:genetics / Q000276:immunology*; D027601:Polyomavirus Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D046888:Tissue Array Analysis
D000906:Antibodies; D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral