title: Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study.
abstract: 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.
  
  
  
  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.
  
  
  
  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%.
  
  
  
  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.
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.|Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington.|Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Kelly G
authors.initials: KG
authors.lastname: Paulson
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Lewis
authors.affiliation: Clinical Statistics, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Mary W
authors.initials: MW
authors.lastname: Redman
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors.forename: William T
authors.initials: WT
authors.lastname: Simonson
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Aaron
authors.initials: A
authors.lastname: Lisberg
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors.forename: Deborah
authors.initials: D
authors.lastname: Ritter
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morishima
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Hutchinson
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Lola
authors.initials: L
authors.lastname: Mudgistratova
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Astrid
authors.initials: A
authors.lastname: Blom
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Jayasri
authors.initials: J
authors.lastname: Iyer
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Ata S
authors.initials: AS
authors.lastname: Moshiri
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Erica S
authors.initials: ES
authors.lastname: Tarabadkar
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Carter
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington.|Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Shailender
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Masaoki
authors.initials: M
authors.lastname: Kawasumi
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Galloway
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Wener
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.|Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Paul
authors.initials: P
authors.lastname: Nghiem
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D015415:Biomarkers; D015266:Carcinoma, Merkel Cell / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D011159:Population Surveillance; D011446:Prospective Studies; D015203:Reproducibility of Results; D016036:Seroepidemiologic Studies; D014412:Tumor Virus Infections / Q000150:complications / Q000276:immunology / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D009856:Oncogene Proteins, Viral
keywords: Merkel cell carcinoma (MCC); Merkel cell polyomavirus (MCPyV); T antigen; oncoprotein; serology; skin cancer