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Cancers
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Merkel Cell Carcinoma: An Update and Review
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Merkel Cell Carcinoma: An Update and Review

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (20 October 2022) | Viewed by 22480

Special Issue Editor

Prof. Dr. Eggert Stockfleth

E-Mail Website
Guest Editor
Department of Dermatology, Venereology and Allergology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstraße 56, 44791 Bochum, Germany
Interests: epidemiology; pathogenesis; risk factors; prevention; diagnosis and treatment of skin cancers (melanoma, and non-melanoma skin cancers); chronic inflammatory skin diseases (psoriasis and hidradenitis suppurativa)

Special Issue Information

Dear Colleagues, 

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a high mortality rate and a high tendency of metastatic spread that mainly affects elderly and immunosuppressed individuals. Up to 80% of MCCs are associated with Merkel cell polyoma virus (MCPyV), which is considered a major causative factor of MCC. In addition, UV radiation is involved in the pathogenesis, as indicated by the frequent occurrence on chronically sun-exposed skin and the detection of UV signature mutations in MCC tumor cells. Although causative functions of MCPyV and UV radiation in MCC development have been revealed, the oncogenic mechanisms in MCC are still poorly understood. Many questions remain unanswered, such as, for instance, what are the cells of origin and what are the reasons for the rather low frequency of MCC, whereas a large proportion of the population is infected with MCPyV. Exploration of carcinogenic mechanisms is of fundamental importance with regard to the development of preventive and therapeutic measures. For advanced cancers that cannot be treated curatively by surgery and/or radiotherapy, no well-established systemic therapy exists. Compared to chemotherapeutic modalities, the treatment of advanced MCC has been improved by the introduction of immune checkpoint inhibitors (ICI). However, as not all patients benefit from ICI therapy, there is a need of biomarkers for both indication and monitoring of ICI treatment. This Special Issue aims to provide an update of MCC research and medical care of MCC patients. We welcome papers addressing epidemiology, pathogenesis, diagnosis, prevention and treatment of MCC, including contributions that outline challenges in the field and approaches to overcome them.

Prof. Dr. Eggert Stockfleth
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Merkel cell
  • nonmelanoma skin cancer
  • polyomavirus
  • T-antigen
  • oncogenic virus
  • carcinogenesis
  • immunotherapy
  • check point inhibitor
  • biomarker

Published Papers (13 papers)

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Editorial

Jump to: Research, Review

4 pages, 189 KiB  
Editorial
Merkel Cell Carcinoma: An Update and Review
by Eggert Stockfleth
Cancers 2023, 15(5), 1534; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15051534 - 28 Feb 2023
Viewed by 1451
Abstract
Merkel cell carcinoma (MCC) is a rare, very aggressive skin cancer with a high mortality rate and a high tendency of metastatic spread [...] Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)

Research

Jump to: Editorial, Review

6 pages, 223 KiB  
Communication
Evolving Applications of Circulating Tumor DNA in Merkel Cell Carcinoma
by Varsha Prakash, Ling Gao and Soo J. Park
Cancers 2023, 15(3), 609; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15030609 - 18 Jan 2023
Cited by 4 | Viewed by 1388
Abstract
Circulating tumor DNA (ctDNA) is a subset of circulating cell-free DNA released by lysed tumor cells that can be characterized by its shorter strand length and tumor genome-specific information. The relatively short half-life of ctDNA allows it to provide a real-time measure of [...] Read more.
Circulating tumor DNA (ctDNA) is a subset of circulating cell-free DNA released by lysed tumor cells that can be characterized by its shorter strand length and tumor genome-specific information. The relatively short half-life of ctDNA allows it to provide a real-time measure of tumor burden which has potential prognostic and surveillance value as a tumor biomarker. Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer that requires close monitoring due to the high risk of relapse. There are currently no good tumor biomarkers for MCC patients, especially those who are negative for Merkel cell polyomavirus. ctDNA shows promise for improving the prognoses of MCC patients by monitoring tumor burden, identifying minimal residual disease (MRD), and stratifying patients by their likelihood of response to immune checkpoint inhibition or risk of relapse. In particular, bespoke ultra-sequencing platforms allow for the creation of patient-specific mutation panels that improve ctDNA detection, especially for patients with rare or uncharacteristic mutations. Leveraging bespoke ctDNA assays may improve physicians’ ability to alter treatment plans for non-responsive or high-risk patients. In addition, ctDNA MRD monitoring may allow physicians to treat relapses early before clinically evident disease is present. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
11 pages, 2583 KiB  
Article
The Antineoplastic Effect of Dimethyl Fumarate on Virus-Negative Merkel Cell Carcinoma Cell Lines: Preliminary Results
by Thilo Gambichler, Lyn G. Brüggestrat, Marina Skrygan, Christina H. Scheel, Laura Susok and Jürgen C. Becker
Cancers 2023, 15(2), 547; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15020547 - 16 Jan 2023
Cited by 1 | Viewed by 1449
Abstract
Merkel cell carcinoma (MCC) is a rare, difficult-to-treat skin cancer once immunotherapy has failed. MCC is associated either with the clonal integration of the Merkel cell polyomavirus (MCPyV) or mutagenic UV-radiation. Fumaric acid esters, including dimethyl fumarate (DMF), have been shown to inhibit [...] Read more.
Merkel cell carcinoma (MCC) is a rare, difficult-to-treat skin cancer once immunotherapy has failed. MCC is associated either with the clonal integration of the Merkel cell polyomavirus (MCPyV) or mutagenic UV-radiation. Fumaric acid esters, including dimethyl fumarate (DMF), have been shown to inhibit cell growth in cutaneous melanoma and lymphoma. We aimed to explore the effects of DMF on MCPyV-negative MCC cell lines. Three MCC cell lines (MCC13, MCC14.2, and MCC26) were treated with different doses of DMF. The cytotoxic effects and cell proliferation were assessed by the MTT cytotoxicity assay and BrdU proliferation assay at different time points. A significant reduction in cell viability and proliferation were demonstrated for all the cell lines used, with DMF proving to be effective. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
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14 pages, 3410 KiB  
Article
Postoperative Radiotherapy and the Role of Regional Lymph Node Irradiation in Localized Merkel Cell Carcinoma: A Single-Center Retrospective Analysis
by Lisa-Antonia Dinges, Tanja Eichkorn, Sebastian Regnery, Juliane Hörner-Rieber, Jürgen Debus, Jessica C. Hassel and Kristin Lang
Cancers 2022, 14(24), 6140; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14246140 - 13 Dec 2022
Cited by 5 | Viewed by 1252
Abstract
The aim of this study was to analyze the pattern of relapse of patients with Merkel cell carcinoma (MCC) that underwent resection of the primary tumor site and postoperative radiotherapy at the Department of Radiation Oncology of Heidelberg University and to determine the [...] Read more.
The aim of this study was to analyze the pattern of relapse of patients with Merkel cell carcinoma (MCC) that underwent resection of the primary tumor site and postoperative radiotherapy at the Department of Radiation Oncology of Heidelberg University and to determine the role of the elective radiotherapy of regional lymph nodes with respect to SLNB results. A total of 57 patients were included in the present retrospective analysis. A total of 33 patients had additional lymph node irradiation (LNI); 24 had postoperative radiotherapy of the tumor bed only. Median follow-up was 43 months. Recurrence rate of the total cohort was 22.8%. Most relapses (69%) occurred in the regional nodes. Cumulative infield-tumor recurrence rate was low with 5.3%. Regional recurrence was more frequent in the cohort without LNI with 85.7% versus 37.5% with LNI. These results were similar for patients with negative sentinel lymph node (SLN) only with 80% regional relapses for those without LNI versus 33% with LNI. In conclusion, our data show that regional recurrence is the most frequent site of relapse in stage I-III MCC treated with curative intended postoperative radiotherapy and that elective irradiation of the regional lymph nodes reduces the risk of regional relapse even if the SLN was negative. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
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16 pages, 1543 KiB  
Article
Management and Prognosis of Cardiac Metastatic Merkel Cell Carcinoma: A Case–Control Study and Literature Review
by Tomoko Akaike, Kelsey Cahill, Gensuke Akaike, Emily T. Huynh, Daniel S. Hippe, Michi M. Shinohara, Jay Liao, Smith Apisarnthanarax, Upendra Parvathaneni, Evan Hall, Shailender Bhatia, Richard K. Cheng, Paul Nghiem and Yolanda D. Tseng
Cancers 2022, 14(23), 5914; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14235914 - 30 Nov 2022
Cited by 2 | Viewed by 1732
Abstract
Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin cancer, has a high rate (20%) of distant metastasis. Within a prospective registry of 582 patients with metastatic MCC (mMCC) diagnosed between 2003–2021, we identified 9 (1.5%) patients who developed cardiac metastatic MCC (mMCC). We [...] Read more.
Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin cancer, has a high rate (20%) of distant metastasis. Within a prospective registry of 582 patients with metastatic MCC (mMCC) diagnosed between 2003–2021, we identified 9 (1.5%) patients who developed cardiac metastatic MCC (mMCC). We compared overall survival (OS) between patients with cardiac and non-cardiac metastases in a matched case–control study. Cardiac metastasis was a late event (median 925 days from initial MCC diagnosis). The right heart was predominantly involved (8 of 9; 89%). Among 7 patients treated with immunotherapy, 6 achieved a complete or partial response of the cardiac lesion. Among these 6 responders, 5 received concurrent cardiac radiotherapy (median 20 Gray) with immunotherapy; 4 of 5 did not have local disease progression or recurrence in the treated cardiac lesion. One-year OS was 44%, which was not significantly different from non-cardiac mMCC patients (45%, p = 0.96). Though it occurs relatively late in the disease course, cardiac mMCC responded to immunotherapy and/or radiotherapy and was not associated with worse prognosis compared to mMCC at other anatomic sites. These results are timely as cardiac mMCC may be increasingly encountered in the era of immunotherapy as patients with metastatic MCC live longer. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
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7 pages, 466 KiB  
Communication
Defining the Profile of Patients with Primary Merkel Cell Carcinoma in Central Italy: A Retrospective Analysis
by Giulio Gualdi, Gerardo Ferrara, Marco Simonacci, Maria Concetta Fargnoli, Laura Sollima, Elisa Molinelli, Anna Campanati, Giampiero Mazzocchetti, Alfredo Giacchetti, Paolo Amerio and on behalf of the Study Group
Cancers 2022, 14(20), 5140; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14205140 - 20 Oct 2022
Cited by 1 | Viewed by 1121
Abstract
Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer that usually occurs in elderly people on sun-exposed areas, with a predisposition to local recurrence. Evidence suggests a growing incidence over the past decade; however, robust epidemiologic data are still lacking. We describe [...] Read more.
Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer that usually occurs in elderly people on sun-exposed areas, with a predisposition to local recurrence. Evidence suggests a growing incidence over the past decade; however, robust epidemiologic data are still lacking. We describe the MCC population in clinical practice in a retrospective analysis of demographic, clinical, and tumor characteristics from medical records of primary MCC patients, between 2015 and 2020, at six dermatology clinics in Central Italy. Ninety-four patients were included (57.4% male; mean age 78.2 ± 10.1 years, range 47–99 years). The estimated incidence rate of MCC was 0.93 per 100,000 inhabitants/year. Lower limbs were the most frequently affected site (31.5%), and 54% of patients for whom information was available were immunosuppressed. Lymph node involvement was reported in 42.5% of patients, and distant metastases in almost 20%. Most patients underwent surgery for tumor excision and were mainly referred to specialized dermatology clinics by dermatologists (47.9%) and general surgeons (28.7%). Apart from the relatively balanced prevalence of MCC in men and women, the predominant location on lower limbs, and the higher incidence rate compared with previous reports in Italy, this population is, overall, similar to the populations described in other observational studies. MCC management requires the involvement of several specialties. Increased awareness of MCC and standardization of its management are urgently needed. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
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12 pages, 922 KiB  
Article
Nodal Merkel Cell Carcinoma with Unknown Primary Site and No Distant Metastasis: A Single-Center Series
by Nicola Fazio, Patrick Maisonneuve, Francesca Spada, Lorenzo Gervaso, Chiara Alessandra Cella, Marta Pozzari, Dario Zerini, Eleonora Pisa, Caterina Fumagalli, Massimo Barberis, Alice Laffi, Chiara Maria Grana C., Gianmarco Orsolini, Pierpaolo Prestianni, Guido Bonomo, Luigi Funicelli, Emilio Bertani, Paola Queirolo, Davide Ravizza, Manila Rubino, Giulio Tosti and Elisabetta Pennacchioliadd Show full author list remove Hide full author list
Cancers 2022, 14(19), 4777; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194777 - 29 Sep 2022
Cited by 5 | Viewed by 1485
Abstract
Merkel cell carcinoma (MCC) is a very rare and aggressive neuroendocrine carcinoma originating from Merkel cells, typically with a skin nodule; however, it exceptionally presents with only a basin lymph node localization, with neither a cutaneous primary site nor distant metastases. From 1996 [...] Read more.
Merkel cell carcinoma (MCC) is a very rare and aggressive neuroendocrine carcinoma originating from Merkel cells, typically with a skin nodule; however, it exceptionally presents with only a basin lymph node localization, with neither a cutaneous primary site nor distant metastases. From 1996 to 2020, among patients with histologically confirmed MCC managed at a neuroendocrine neoplasm-referral center, we selected those with an exclusive nodal basin, no distant metastasis, and an unknown primary site defined by cross-sectional and physical examination. A total of 55 out of 310 patients fulfilled the selection criteria. The median age was 64 years and the majority were males. Inguinal lymph-nodes were the most common anatomic site. With a median follow-up of 4.3 years, the 5-year relapse-free survival (RFS) rate was 56.6 (95% CI 42.0–68.8%) and the 5-year cancer specific survival (CSS) rate was 68.5 (95% CI 52.8–79.9%) for the whole population. The 36 patients (65.5%) undergoing lymphadenectomy (LND) + radiotherapy (RT) ± chemotherapy had a 5-year RFS rate of 87.2% (95% CI 65.5–95.7%) and a 5-year CSS rate of 90.5% (95% CI 67.0–97.5), which were better than those receiving LND alone. In a multivariable analysis, the survival benefit for LND + RT remained significant. Results from one of the largest single-center series of nMCC-UP suggest that a curative approach including RT can be effective, similar to what is observed for stage IIIB MCC. Multicentric studies with homogenous populations should be carried out in this controversial clinical entity, to minimize the risk of biases and provide robust data. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
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16 pages, 976 KiB  
Article
Activation of Oncogenic and Immune-Response Pathways Is Linked to Disease-Specific Survival in Merkel Cell Carcinoma
by Benjamin Sundqvist, Sami Kilpinen, Tom Böhling, Virve Koljonen and Harri Sihto
Cancers 2022, 14(15), 3591; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14153591 - 23 Jul 2022
Cited by 8 | Viewed by 1910
Abstract
Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin with a poor prognosis. Improving the prognosis of MCC by means of targeted therapies requires further understanding of the mechanisms that drive tumor progression. In this study, [...] Read more.
Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin with a poor prognosis. Improving the prognosis of MCC by means of targeted therapies requires further understanding of the mechanisms that drive tumor progression. In this study, we aimed to identify the genes, processes, and pathways that play the most crucial roles in determining MCC outcomes. Methods: We investigated transcriptomes generated by RNA sequencing of formalin-fixed paraffin-embedded tissue samples of 102 MCC patients and identified the genes that were upregulated among survivors and in patients who died from MCC. We subsequently cross-referenced these genes with online databases to investigate the functions and pathways they represent. We further investigated differential gene expression based on viral status in patients who died from MCC. Results: We found several novel genes associated with MCC-specific survival. Genes upregulated in patients who died from MCC were most notably associated with angiogenesis and the PI3K-Akt and MAPK pathways; their expression predominantly had no association with viral status in patients who died from MCC. Genes upregulated among survivors were largely associated with antigen presentation and immune response. Conclusion: This outcome-based discrepancy in gene expression suggests that these pathways and processes likely play crucial roles in determining MCC outcomes. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
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9 pages, 2352 KiB  
Article
The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis
by Konstantin Drexler, Barbara Schwertner, Silke Haerteis, Thiha Aung, Mark Berneburg, Edward K. Geissler, Maria E. Mycielska and Sebastian Haferkamp
Cancers 2022, 14(14), 3425; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143425 - 14 Jul 2022
Cited by 4 | Viewed by 1385
Abstract
Merkel cell carcinoma (MCC) is a rare but highly aggressive tumor of the skin with a poor prognosis. The factors driving this cancer must be better understood in order to discover novel targets for more effective therapies. In the search for targets, we [...] Read more.
Merkel cell carcinoma (MCC) is a rare but highly aggressive tumor of the skin with a poor prognosis. The factors driving this cancer must be better understood in order to discover novel targets for more effective therapies. In the search for targets, we followed our interest in citrate as a central and critical metabolite linked to fatty acid synthesis in cancer development. A key to citrate uptake in cancer cells is the high expression of the plasma membrane citrate transporter (pmCiC), which is upregulated in the different adenocarcinoma types tested so far. In this study, we show that the pmCiC is also highly expressed in Merkel cell carcinoma cell lines by western blot and human tissues by immunohistochemistry staining. In the presence of extracellular citrate, MCC cells show an increased proliferation rate in vitro; a specific pmCiC inhibitor (Na+-gluconate) blocks this citrate-induced proliferation. Furthermore, the 3D in vivo Chick Chorioallantoic Membrane (CAM) model showed that the application of Na+-gluconate also decreases Merkel cell carcinoma growth. Based on our results, we conclude that pmCiC and extracellular citrate uptake should be considered further as a potential novel target for the treatment of Merkel cell carcinoma. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
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14 pages, 1221 KiB  
Article
Treatment of Locally Advanced Merkel Cell Carcinoma—A Multi-Center Study
by Monika Dudzisz-Sledz, Paweł Sobczuk, Katarzyna Kozak, Tomasz Switaj, Hanna Kosela-Paterczyk, Anna Malgorzata Czarnecka, Slawomir Falkowski, Paweł Rogala, Tadeusz Morysinski, Mateusz Jacek Spalek, Marcin Zdzienicki, Tomasz Goryn, Marcin Zietek, Bozena Cybulska-Stopa, Stanisław Klek, Grazyna Kaminska-Winciorek, Barbara Ziolkowska, Anna Szumera-Cieckiewicz and Piotr Rutkowski
Cancers 2022, 14(2), 422; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14020422 - 14 Jan 2022
Cited by 4 | Viewed by 2248
Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a high risk of recurrence and poor prognosis. The treatment of locally advanced disease involves surgery and radiotherapy. To analyze real-life treatment patterns and clinical outcomes, we conducted a retrospective analysis of [...] Read more.
Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a high risk of recurrence and poor prognosis. The treatment of locally advanced disease involves surgery and radiotherapy. To analyze real-life treatment patterns and clinical outcomes, we conducted a retrospective analysis of data from 161 MCC patients treated with curative intent in four oncological centers in Poland. The median age at diagnosis was 72 years (30–94); 49.7% were male. Lymph node (LN) involvement at diagnosis was found in 26.9% of patients. Sentinel lymph node biopsy (SLNB) was performed in 36.5% of patients (positive in 10.5%), and 51.9% of patients received perioperative treatment. The relapse rate was 38.3%. With the median follow-up of 2.3 years, the median disease-free survival (DFS) was not reached, and the 1-year rate was 65%. The negative independent risk factors for DFS were male gender, metastases in LN at diagnosis, no SLNB in patients without clinical nodal metastases, and no perioperative radiotherapy. The estimated median overall survival (OS) was 6.9 years (95% CI 4.64–9.15). The negative independent risk factors for OS were male gender, age above 70, metastases in LN at diagnosis, and no SLNB in patients without clinical nodal metastases. Our results confirm that the MCC treatment should be conducted in an experienced multidisciplinary team; however, the outcomes are still unsatisfactory. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
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Review

Jump to: Editorial, Research

18 pages, 3540 KiB  
Review
Epidemiology of Merkel Cell Polyomavirus Infection and Merkel Cell Carcinoma
by Steffi Silling, Alexander Kreuter, Thilo Gambichler, Thomas Meyer, Eggert Stockfleth and Ulrike Wieland
Cancers 2022, 14(24), 6176; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14246176 - 14 Dec 2022
Cited by 9 | Viewed by 2150
Abstract
Merkel cell polyomavirus (MCPyV) is a ubiquitous virus replicating in human dermal fibroblasts. MCPyV DNA can be detected on healthy skin in 67–90% of various body sites, and intact virions are regularly shed from the skin. Infection occurs early in life, and seropositivity [...] Read more.
Merkel cell polyomavirus (MCPyV) is a ubiquitous virus replicating in human dermal fibroblasts. MCPyV DNA can be detected on healthy skin in 67–90% of various body sites, and intact virions are regularly shed from the skin. Infection occurs early in life, and seropositivity increases from 37 to 42% in 1- to 6-year-olds to 92% in adults. Merkel cell carcinoma (MCC) is a rare but very aggressive neuroendocrine tumor of the skin. It develops mainly on sun-exposed areas as a fast-growing, reddish nodule. Two MCC entities exist: about 80% of MCC are MCPyV-associated. Tumorigenesis is driven by viral integration into the host genome and MCPyV oncogene expression. In MCPyV-negative MCC, UV radiation causes extensive DNA damage leading to the deregulation of the cell cycle. In recent decades, MCC incidence rates have increased worldwide, e.g., in the United States, from 0.15 in 1986 to 0.7/100,000 in 2016. Risk factors for the development of MCC include male sex, older age (>75 years), fair skin, intense UV exposure, and immunosuppression. Projections suggest that due to aging populations, an increase in immunosuppressed patients, and enhanced UV exposure, MCC incidence rates will continue to rise. Early diagnosis and prompt treatment are crucial to reducing high MCC morbidity and mortality. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
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19 pages, 1864 KiB  
Review
T-Cell Mediated Immunity in Merkel Cell Carcinoma
by Kelsey Ouyang, David X. Zheng and George W. Agak
Cancers 2022, 14(24), 6058; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14246058 - 09 Dec 2022
Cited by 2 | Viewed by 1854
Abstract
Merkel cell carcinoma (MCC) is a rare and frequently lethal skin cancer with neuroendocrine characteristics. MCC can originate from either the presence of MCC polyomavirus (MCPyV) DNA or chronic ultraviolet (UV) exposure that can cause DNA mutations. MCC is predominant in sun-exposed regions [...] Read more.
Merkel cell carcinoma (MCC) is a rare and frequently lethal skin cancer with neuroendocrine characteristics. MCC can originate from either the presence of MCC polyomavirus (MCPyV) DNA or chronic ultraviolet (UV) exposure that can cause DNA mutations. MCC is predominant in sun-exposed regions of the body and can metastasize to regional lymph nodes, liver, lungs, bone, and brain. Older, light-skinned individuals with a history of significant sun exposure are at the highest risk. Previous studies have shown that tumors containing a high number of tumor-infiltrating T-cells have favorable survival, even in the absence of MCPyV DNA, suggesting that MCPyV infection enhances T-cell infiltration. However, other factors may also play a role in the host antitumor response. Herein, we review the impact of tumor infiltrating lymphocytes (TILs), mainly the CD4+, CD8+, and regulatory T-cell (Tregs) responses on the course of MCC, including their role in initiating MCPyV-specific immune responses. Furthermore, potential research avenues related to T-cell biology in MCC, as well as relevant immunotherapies are discussed. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
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20 pages, 1029 KiB  
Review
Merkel Cell Polyomavirus (MCPyV) and Cancers: Emergency Bell or False Alarm?
by Maria Georgia Dimitraki and George Sourvinos
Cancers 2022, 14(22), 5548; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14225548 - 11 Nov 2022
Cited by 3 | Viewed by 1723
Abstract
Merkel cell polyomavirus (MCPyV), the sole member of Polyomavirus associated with oncogenesis in humans, is the major causative factor of Merkel cell carcinoma (MCC), a rare, neuroendocrine neoplasia of the skin. Many aspects of MCPyV biology and oncogenic mechanisms remain poorly understood. However, [...] Read more.
Merkel cell polyomavirus (MCPyV), the sole member of Polyomavirus associated with oncogenesis in humans, is the major causative factor of Merkel cell carcinoma (MCC), a rare, neuroendocrine neoplasia of the skin. Many aspects of MCPyV biology and oncogenic mechanisms remain poorly understood. However, it has been established that oncogenic transformation is the outcome of the integration of the viral genome into the host DNA. The high prevalence of MCPyV in the population, along with the detection of the virus in various human tissue samples and the strong association of MCPyV with the emergence of MCC, have prompted researchers to further investigate the role of MCPyV in malignancies other than MCC. MCPyV DNA has been detected in several different non-MCC tumour tissues but with significantly lower prevalence, viral load and protein expression. Moreover, the two hallmarks of MCPyV MCC have rarely been investigated and the studies have produced generally inconsistent results. Therefore, the outcomes of the studies are inadequate and unable to clearly demonstrate a direct correlation between cellular transformation and MCPyV. This review aims to present a comprehensive recapitulation of the available literature regarding the association of MCPyV with oncogenesis (MCC and non-MCC tumours). Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: An Update and Review)
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