Viral Oncoprotein Antibodies as a Marker for Recurrence of Merkel Cell Carcinoma: A Prospective Validation Study

December 7, 2016



Publication Date

December 7, 2016


Paulson K, Lewis C, Redman M, Simonson W, Lisberg A, Ritter D, Morishima C, Hutchinson K, Mudgistratova L, Blom A, Iyer J, Moshiri A, Tarabadkar E, Carter J, Bhatia S, Kawasumi M, Galloway D, Wener M, Nghiem P

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Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases per year in the United States, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV oncoprotein (T-antigens) have been correlated with MCC tumor burden. The present study assesses the clinical utility of MCPyV-oncoprotein antibody titers for MCC prognostication and surveillance.

Methods: MCPyV-oncoprotein antibody detection was optimized in a clinical laboratory. A cohort of 219 patients with newly diagnosed MCC were followed prospectively (median follow-up, 1.9 years). Among the seropositive patients, antibody titer and disease status were serially tracked.

Results: Antibodies to MCPyV oncoproteins were rare among healthy individuals (1%) but were present in most patients with MCC (114 of 219 patients [52%]; P<.01). Seropositivity at diagnosis
independently predicted decreased recurrence risk (hazard ratio, 0.58; P5.04) in multivariate analyses adjusted for age, sex, stage, and immunosuppression. After initial treatment, seropositive patients whose disease did not recur had rapidly falling titers that became negative by a median of 8.4 months. Among seropositive patients who underwent serial evaluation (71 patients; 282 time
points), an increasing oncoprotein titer had a positive predictive value of 66% for clinically evident recurrence, whereas a decreasing titer had a negative predictive value of 97%.

Conclusions: Determination of oncoprotein antibody titer assists in the clinical management
of patients with newly diagnosed MCC by stratifying them into a higher risk seronegative cohort, in which radiologic imaging may play a more prominent role, and into a lower risk seropositive cohort, in which disease status can be tracked in part by oncoprotein antibody titer. Cancer 2016;000:000–000. VC 2016 American Cancer Society.

Keywords: Merkel cell carcinoma (MCC), Merkel cell polyomavirus (MCPyV), oncoprotein, serology, skin cancer, T antigen.