Antibodies to Merkel cell polyomavirus and intratumoral CD8+ lymphocyte invasion predict outcomes in patients with MCC.

Merkel cell carcinoma (MCC) is a rare, highly lethal, cutaneous neuroendocrine carcinoma with a rapidly rising worldwide incidence. Risk factors include advanced age, history of ultraviolet exposure, and immunosuppression. Although the Merkel cell polyomavirus (MCPyV) is commonly found in normal skin of unaffected individuals, the virus is genomically integrated into early tumors, expresses a mutated T antigen that retains oncogenic activity, and is necessary to the survival and proliferation of MCC cell lines. The evidence points to a causal role for MCPyV in MCC development. Until now, immune responses to MCC and MCPyV have not been correlated with outcome. Two recent investigations examine factors related to prognosis.


Touzé and colleagues compared levels of MCPyV antibodies with outcomes in 68 patients with MCC. They found significantly higher titers of capsid protein VP1 in patients than in normal controls. Antibody levels did not correlate with tumor size, nodal status, immune deficiency, viral load, period of sampling, or treatment, but high levels predicted lower nodal and metastatic recurrence (mean recurrence-free period, 26.1 months in those with titers >10,000 vs. 12.1 months in those with titers <10,000).

Paulson and colleagues performed transcriptomic analysis of 35 MCCs. They found a correlation between the density of CD8+ peritumoral and intratumoral infiltrating lymphocytes and CD8 mRNA expression. In 146 additional patients, they found 100% disease-specific survival at 5 years in patients with about 60 or more CD8+ cells per high-powered field, compared with 60% in patients with lower counts.


Citation(s):

Touzé A et al. High levels of antibodies against Merkel cell polyomavirus identify a subset of patients with Merkel cell carcinoma with better clinical outcome. J Clin Oncol 2011 Apr 20; 29:1612.

Paulson KG et al. Transcriptome-wide studies of Merkel cell carcinoma and validation of intratumoral CD8+ lymphocyte invasion as an independent predictor of survival. J Clin Oncol 2011 Apr 20; 29:1539.