Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study: Viral Oncoprotein Antibodies in MCC

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Abstract

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; P = .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. Cancer2017;123:1464–1474. © 2016 American Cancer Society.

CONCLUSIONS:

More than 40% of patients who are diagnosed with virally associated Merkel cell carcinoma will develop recurrent disease. In this report, a Merkel cell polyomavirus oncoprotein antibody titer is clinically useful in patients with newly diagnosed Merkel cell carcinoma, because it identifies 2 groups: antibody-negative patients, who have a higher risk of recurrence, and antibody-positive patients, in whom the ability of this test to serve as a serial tumor marker is prospectively validated with high sensitivity and specificity.

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