Abstract C237: Merkel cell polyomavirus infection-related Merkel cell carcinomas have intratumoral lymphocyte infiltrates and favorable survival.

Abstract

Abstract Introduction: Merkel cell carcinoma (MCC) is rare and often aggressive skin cancer that manifests mainly in elderly white people. The majority of MCCs contain Merkel cell polyomavirus (MCPyV) DNA. Patients with MCPyV-positive MCC have favorable survival as compared to those with MCPyV-negative tumor. The reasons for this remain speculative, but host immune defence might influence outcome of patients with MCPyV infection. Material and Methods: Tumor infiltrating T-lymphocytes (CD3+ cells) and macrophages (CD68+ cells) were stained using immunohistochemistry from 116 MCCs. The numbers of stained cells were counted at 400× magnification of the microscope. Presence of MCPyV infection was assessed by detecting MCPyV DNA using quantitative PCR and the viral large T antigen using immunohistochemistry. The associations between the tumor immune cell counts, presence of MCPyV DNA, clinicopatholocial factors and patient survival were examined using the Mann-Whitney test and the Kaplan-Meyer survival analysis. Results: MCPyV-positive tumors contained more CD3+ and CD68+ cells as compared to MCPyV-negative cancers (5.3 vs. 3.3 cells/high-power field [HPF], p=0.014; and 5.3 vs. 4.0 cells/HPF, p=0.028, respectively). Similar results were obtained when presence of MCPyV infection was efined by expression of the viral large T-antigen (5.9 vs. 2.7 cells/HPF, p<0.001; and 5.6 vs. 3.9 cells/HPF, p=0.003, respectively). Patients with regional nodal metastases had fewer CD3+ cells in the primary tumor as compared to those without metastases (2.3 vs. 5.3 cells/HPF, p=0.006). Patients who had MCC with a higher than the median number of CD3+ cells had better MCC-specific survival (55.2% vs. 82.1%, log-rank test p=0.003) and overall survival (22.4% vs. 50.0%, p=0.002) as compared to those with a smaller than the median tumor CD3+ cell count. Tumor CD3+ count was an independent prognostic factor for overall survival in a Cox multivariable analysis that included the presence of regional nodal etastases, gender and MCPyV large T-antigen expression as covariates (HR=0.55, 95% CI, 0.35 to 0.88, p=0.012). Conclusions: MCCs with evidence of MCPyV infection harbor high numbers of tumor infiltrating T-lymphocytes. A high number of CD3+ cells in the tumor is associated with generally favorable survival. Host immune response to MCPyV might explain in part the favorable survival associated with MCCs with MCPyV infection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C237.