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      Expression of Merkelcell polyomavirus (MCPyV) large T-antigen in Merkel cell carcinoma lymph node metastases predicts poor outcome

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          Abstract

          Background

          The aim of this study was to determine the prevalence of MCPyV in Merkel cell carcinoma (MCC) primaries versus lymph node metastasis and to evaluate possible prognostic factors.

          Methods

          Samples of MCC primaries and lymph node metastases were stained immunohistochemically for the MCPyV large T-antigen and expression was compared to patients´ clinical outcome.

          Results

          41 MCC patients were included. 33 (61%) out of 54 specimens were MCPyV-positive in the immunohistochemistry. 15 (47%) out of 32 primary tumors were positive compared to 18 (82%) out of 22 lymph node metastases. Eleven patients with positive polyomavirus expression died from the carcinoma compared to 4 patients without virus expression. Cox regression analysis showed worse disease-free survival in patients with MCPyV compared to virus-negative lymph nodes (p = 0.002).

          Conclusions

          To our knowledge this is the first study to describe a negative prognostic effect of the MCPyV expression in lymph node metastasis in MCC patients.

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          Most cited references19

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          Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays.

          Merkel cell polyomavirus (MCV) is a newly-discovered human tumor virus found in approximately 80% of Merkel cell carcinoma (MCC). The rate of MCV infection among persons without MCC is unknown. We developed a MCV virus-like particle (VLP) enzyme-linked immunoassay (EIA) that does not cross-react with human BK or murine polyomaviruses. Peptide mapping of the MCV VP1 gene and immunoblotting with denatured MCV VLP are less sensitive than the MCV EIA in detecting MCV antibodies suggesting antibody reactivity in this assay primarily targets conformational but not linear epitopes. Among MCC patients, all 21 (100%) patients tested with MCV-positive tumors had high serum MCV IgG but not high MCV IgM levels. Only 3 of 6 (50%) MCC patients with MCV-negative tumors were positive for MCV antibodies. Sera from most adults, including 107 of 166 (64%) blood donors, 63 of 100 (63%) commercial donors and 37 of 50 (74%) systemic lupus erythematosus patients, show evidence for prior MCV exposure. Age-specific MCV prevalence was determined by examining a cross-sectional distribution of 150 Langerhans cell histiocytosis (an unrelated neoplasm) patient sera. MCV prevalence increases from 50% among children age 15 years or younger to 80% among persons older than 50 years. We did not find evidence for vertical transmission among infants. Although past exposure to MCV is common among all adult groups, MCC patients have a markedly elevated MCV IgG response compared with control patients. Our study demonstrates that MCV is a widespread but previously unrecognized human infection. 2009 UICC
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            Trabecular carcinoma of the skin.

            C. Toker (1971)
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              MC polyomavirus is frequently present in Merkel cell carcinoma of European patients.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 August 2017
                2017
                : 12
                : 8
                : e0180426
                Affiliations
                [1 ] Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, Austria
                [2 ] Department of Surgery, Clinical Division of Plastic and Reconstructive Surgery, Medical University of Vienna, Vienna, Austria
                [3 ] Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria
                [4 ] Department of Dermatology, Research Division of Biology and Pathobiology of the Skin, Medical University of Vienna, Vienna, Austria
                [5 ] Department of Dermatology, Medical University of Wuerzburg, Wuerzburg, Germany
                Fu Jen Catholic University, TAIWAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: GH AF JP BE.

                • Data curation: GH BE.

                • Formal analysis: HS MG BE.

                • Funding acquisition: BE.

                • Investigation: GH AF HS LN.

                • Methodology: GH AF JP HS BE MM.

                • Project administration: BE.

                • Resources: SJ AF JP HS LN MM RH.

                • Software: GH JP HS BE.

                • Supervision: BE.

                • Validation: GH SJ AF JP HS LN MM RH MG BE.

                • Visualization: GH MM MG BE.

                • Writing – original draft: GH LN BE.

                • Writing – review & editing: GH SJ AF JP HS LN MM RH MG BE.

                Author information
                http://orcid.org/0000-0002-2464-6856
                Article
                PONE-D-16-38667
                10.1371/journal.pone.0180426
                5538748
                28763479
                4d843bc1-f526-4ccb-a57d-12f736edcc5d
                © 2017 Haymerle et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 September 2016
                : 17 May 2017
                Page count
                Figures: 4, Tables: 2, Pages: 11
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Lymphatic System
                Lymph Nodes
                Medicine and Health Sciences
                Anatomy
                Lymphatic System
                Lymph Nodes
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Carcinomas
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Epithelial Cells
                Merkel Cells
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Epithelium
                Epithelial Cells
                Merkel Cells
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Epithelium
                Epithelial Cells
                Merkel Cells
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Research and Analysis Methods
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Research and Analysis Methods
                Biological Cultures
                Cell Cultures
                Cultured Tumor Cells
                Carcinoma Cells
                Research and Analysis Methods
                Histochemistry and Cytochemistry Techniques
                Immunohistochemistry Techniques
                Research and Analysis Methods
                Immunologic Techniques
                Immunohistochemistry Techniques
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Metastatic Tumors
                Biology and Life Sciences
                Anatomy
                Head
                Medicine and Health Sciences
                Anatomy
                Head
                Custom metadata
                All relevant data are within the paper.

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