Antibodies to Merkel Cell Polyomavirus T Antigen Oncoproteins Reflect Tumor Burden in Merkel Cell Carcinoma Patients

October 19, 2010

Publisher

American Association for Cancer Research

Publication Date

October 19, 2010

Authors

Kelly G. Paulson, Joseph J. Carter, Lisa G. Johnson, Kevin W. Cahill, Jayasri G. Iyer, David Schrama, Juergen C. Becker, Margaret M. Madeleine, Paul Nghiem, Denise A. Galloway

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Merkelcell.org Summary

A portion of the Merkel cell polyomavirus called the “T-antigen” (t is for tumor) is present in about 80% of all MCC tumors. This protein is critical for most MCC tumors to grow. In 2010, we reported that antibodies that recognize this T-antigen are present in about 50% of newly diagnosed MCC patients but are almost never present (<1%) in people without MCC (even though 50% of all people have this virus on their skin at any time). More importantly, the levels of these antibodies to the T-antigen decrease rapidly after the cancer is removed from a patient by surgery, radiation therapy, or chemotherapy. By one year after effective treatment, antibody levels are down by about 90%, and continue to fall until they eventually become undetectable. In contrast, if the cancer returns, antibody levels rise rapidly among patients who had antibodies at the time of their original cancer. By comparing the antibody levels at two time points, we can see if the cancer is in remission (falling or undetectable antibody levels) or is returning (rising levels). This test is not useful in patients who did not have antibodies at the time of their original cancer as they also do not make them after the cancer returns.

Abstract

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.

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