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Cancer. 2017 Apr 15;123(8):1464-1474. doi: 10.1002/cncr.30475. Epub 2016 Dec 7.

Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study.

Author information

1
Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.
2
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington.
3
Seattle Cancer Care Alliance, Seattle, Washington.
4
Clinical Statistics, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
5
Department of Laboratory Medicine, University of Washington, Seattle, Washington.
6
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.

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. Cancer 2017;123:1464-1474. © 2016 American Cancer Society.

KEYWORDS:

Merkel cell carcinoma (MCC); Merkel cell polyomavirus (MCPyV); T antigen; oncoprotein; serology; skin cancer

PMID:
27925665
PMCID:
PMC5384867
DOI:
10.1002/cncr.30475
[Indexed for MEDLINE]
Free PMC Article

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