Tumor Ulceration, Reduced Infiltration of CD8-Lymphocytes, High Neutrophil-to-CD8-Lymphocyte Ratio and Absence of MC Virus are Negative Prognostic Markers for Patients with Merkel Cell Carcinoma
Open Access
- 6 April 2020
- Vol. 12 (4), 888
- https://doi.org/10.3390/cancers12040888
Abstract
(1) Background: Merkel cell carcinoma (MCC) is caused by the Merkel cell polyomavirus and UV radiation. Understanding of the underlying biology is limited, but identification of prognostic markers may lead to better prognostic stratification for the patients. (2) Methods: Ninety patients diagnosed with MCC (1996–2012) were included. Virus status was estimated by polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Ulceration status, PD-L1, cd66b neutrophils, cd8 lymphocytes and biomarkers of vascularization (cd34 endothelial cells) and migration (e-cadherin) were estimated by IHC and analyzed with digital pathology. (3) Results: Virus was present in 47% of patient samples and correlated with lower E-cadherin expression (p = 0.0005), lower neutrophil-to-CD8 lymphocyte ratio (N:CD8 ratio) (p = 0.02) and increased PD-L1 expression (p = 0.03). Ulceration was associated with absence of virus (p = 0.03), increased neutrophil infiltration (p < 0.0001) and reduced CD8 lymphocyte infiltration (p = 0.04). In multivariate analysis, presence of virus (p = 0.01), ulceration (p = 0.05) and increased CD8 lymphocyte infiltration (p = 0.001) showed independent prognostic impacts on MCC-specific survival. (3) Conclusions: In this study, we found that a high N:CD8 ratio, ulceration, virus-negative status and absence of CD8 lymphocytes are negative prognostic markers. Accurate prognostic stratification of the patients may be important in the clinical setting for determination of adjuvant treatment.This publication has 50 references indexed in Scilit:
- Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirusJCI Insight, 2012
- Tumor Infiltrating Immune Cells and Outcome of Merkel Cell Carcinoma: A Population-Based StudyClinical Cancer Research, 2012
- Colocalization of Inflammatory Response with B7-H1 Expression in Human Melanocytic Lesions Supports an Adaptive Resistance Mechanism of Immune EscapeScience Translational Medicine, 2012
- Transcriptome-Wide Studies of Merkel Cell Carcinoma and Validation of Intratumoral CD8+ Lymphocyte Invasion As an Independent Predictor of SurvivalJournal of Clinical Oncology, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Merkel Cell Polyomavirus and Two Previously Unknown Polyomaviruses Are Chronically Shed from Human SkinCell Host & Microbe, 2010
- The basics of epithelial-mesenchymal transitionJCI Insight, 2009
- Merkel Cell Polyomavirus Is More Frequently Present in North American than Australian Merkel Cell Carcinoma TumorsJournal of Investigative Dermatology, 2009
- Ultraviolet B Suppresses Immunity by Inhibiting Effector and Memory T CellsThe American Journal of Pathology, 2008
- Clonal Integration of a Polyomavirus in Human Merkel Cell CarcinomaScience, 2008