PROGNOSTIC ROLE OF PD-L1 EXPRESSION AND PRESENCE OF POLYOMAVIRUS IN MERKEL CELL CARCINOMA

Introduction: Merkel cell carcinoma (MCC) is a rare malignant primary skin tumor with neuroendocrine differentiation. Recently, agents blocking the PD-1/PD-L1 pathway have shown objective, durable tumor regressions in patients with advanced solid malignancies. Purpose: This study aimed to describe the clinical, epidemiological and histopathological characteristics of MCC patients, in addition to assessing the prevalence of PD-L1 expression and polyomavirus, as well as defining their prognostic role. Methods: Retrospective study evaluating patients diagnosed with MCC between 1996 and 2019, at a reference cancer center in Rio de Janeiro. Immunohistochemistry tests were performed for Merkel cell Polyomavirus (MCPyV) and PD-L1 in tumor samples. Survival analyzes were performed using the Kaplan-Meier method and the curves were compared using the log-rank test. The raw hazard ratios and respective 95% confidence intervals were estimated by individual semiparametric Cox models. Statistical analyzes were performed in the R package version 4.1.2. Results: A total of 65 patients were included. The mean age at diagnosis was 72 years, 56.9% of the patients were male, 86.2% white, 57.8% illiterate or with incomplete elementary school. The immunohistochemistry for MCPyV was positive in 29 cases (44.6%). In 23 cases (35.4%) the PD-L1 positivity was < 1% and in 42 cases (64.6%) it was ≥ 1%. The MCPyV positive tumor correlates with a greater number of cases of PD-L1 expression ≥ 1%. The analysis was similar with PD-L1 as a dichotomous variable (<5% and ≥5%). In the multivariate analysis, only education (HR = 2.29, 95% CI 1.19 to 4.41, p=0.013) and advanced stage (HR = 3.36, 95% CI 1.58 to 7, 18, p=0.002) had statistically significant worse progression-free survival (PFS). Regarding overall survival (OS), only males (HR = 2.30, 95% CI 1.14 to 4.67, p=0.021), low education (HR = 2.13, 95% CI 1.09 to 4,19, p=0.028) and advanced stage (HR = 3.31, 95% CI 1.54 to 7.09, p=0.002) were risk factors. The estimated OS at 60 months for stages I to III was 48.9% (95% CI 35.9% to 66.2%) and for stage IV was only 8.9% (95% CI 1.4% to 56%). Conclusion: Low education and advanced staging are risk factors for worse PFS and OS. Male sex is also a risk factor for worse OS. The MCPyV positive tumor correlates with a high expression of PD-L1. There was no correlation with survival between MCPyV infection or the percentage of PD-L1 positivity in the present study.