Merkel cell polyomavirus in Merkel cell carcinoma: pilot project to develop biomarkers for validation in a subsequent clinical trial


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Simon Chanas1, David Blackbourn1, Rachel Wheat1, Ditte Hedegaard1, Claudia Roberts2, Naiem Moiemen2, Margaret Sherman2, Mark Pritchard1, Jane Steele1, Jeremy Marsden2, Neil Steven1

1University of Birmingham, UK, 2University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

Abstract

Proffered paper presentation

Background
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer, often associated with immunosuppression. In 2008 a novel mammalian polyomavirus, Merkel cell polyomavirus (MCPyV), was identified integrated into the genome of malignant MCC cells in eight out of ten patients from the USA, a finding since confirmed in France and Germany. A planned UK randomized phase II trial of adjuvant chemotherapy in MCC presents the opportunity to establish a national MCC tissue collection. We undertook a pilot study to determine whether MCPyV was detectable in MCC in a UK population.

Methods
DNA was extracted from archived paraffin fixed tissue specimens, from frozen tissue, from plasma and from peripheral blood mononuclear cells. MCPyV was sought using polymerase chain reaction (PCR), included a nested PCR assay. Four primer sets were based on the published MCPyV sequence. Viral identity was confirmed by sequencing. Approval for this study was granted by Trent Research Ethics Committee.

Results
Using paraffin fixed tissue, MCPyV was identified in 4/11 samples of MCC tissue (36%), 0/4 samples of uninvolved skin form MCC specimens, 0/5 non-MCC skin tumours, 0/1 normal skin. One patient provided a fresh MCC specimen. This was a large lesion with satellites. MCPyV was identified in both MCC and in adjacent skin that was macroscopically normal. Four patients to date have provided blood samples, one at the time of active disease. MCPyV was identified in none of these.

Conclusions
MCPyV is detected in association with MCC in a UK population. The rarity of MCC limits single-centre pilot work in this disease. A national tissue collection is being planned in conjunction with a phase II trial of chemotherapy on behalf of the NCRI Clinical Studies Group. Future work will investigate the epidemiology of MCPyV, its role in MCC aetiology and its potential as a therapeutic target.