Abstract:
BACKGROUND:Merkel cell carcinoma (MCC) is a neuroendocrine cancer of the skin postulated to originate through Merkel cell polyomavirus (MCPyV) oncogenesis and/or by mutations in molecules implicated in the regulation of cell growth and survival. Despite the fact that MCPvV is detected more broadly within the population, only a part of the infected people also develop MCC. It is thus conceivable that together, virus and for example mutations, are necessary for disease development. However, apart from a correlation between MCPyV positivity or mutations and MCC development, less is known about the association of these factors with progressive disease. OBJECTIVES:To analyze MCPyV positivity, load and integration in MCC as well as presence of mutations in PDGFRα and TP53 genes and correlate these with clinical features and disease progression to identify features with prognostic value for clinical progression. METHODS:This is a study on a MCC population group of 64 patients. MCPyV positivity, load and integration in parallel to mutations in the PDGFRα and TP53 were analyzed on genomic DNA from MCC specimens. In addition, expression of PDGFRα, survivin and p53 proteins was analyzed by immunodetection in tissues specimens. All these parameters were analyzed as function of patient's disease progression status. RESULTS:83% of MCCs were positive for the MCPyV and among these 36% also displayed virus-T integration. Viral load ranged from 0.006 to 943 viral DNA copies/β-globin gene and was highest in patients with progressive disease. We detected more than one mutation within the PDGFRα gene and identified two new SNPs in 36% of MCC patients, whereas no mutations were found in TP53 gene. Survivin was expressed in 78% of specimens. We could not correlate either mutations in PDGFR or expression of PDGFR, p53 and surviving either to the disease progression or to the MCPyV positivity. CONCLUSIONS:In conclusion, our data indicate that the viral positivity when associated with high viral load, correlates with poor disease outcome. Frequent mutations in the PDGFRα gene and high survivin expression were found in MCC independent of the viral positivity. These data suggest that these three factors independently contribute to Merkel cell carcinoma development and that only the viral load can be used as indicator of disease progression in virus positive patients.
journal_name
J Dermatol Scijournal_title
Journal of dermatological scienceauthors
Batinica M,Akgül B,Silling S,Mauch C,Zigrino Pdoi
10.1016/j.jdermsci.2015.04.002subject
Has Abstractpub_date
2015-07-01 00:00:00pages
43-9issue
1eissn
0923-1811issn
1873-569Xpii
S0923-1811(15)00150-4journal_volume
79pub_type
杂志文章abstract::Autosomal recessive congenital ichthyoses (ARCI) include several severe subtypes including harlequin ichthyosis (HI), lamellar ichthyosis and non-bullous congenital ichthyosiform erythroderma. Patients with these severe types of ichthyoses frequently show severe hyperkeratosis and scales over a large part of the body ...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
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abstract::Matrix metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. Enhanced expression of matrix metalloproteinase-2 (MMP-2) has been demonstrated in dermatofibroma (DF) and malignant fibrous histiocytoma (MFH). MMP-2 has been shown to be activated by membrane-type MMPs (MT-MMPs). To study the r...
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abstract::SV-40 transformed human keratinocytes (SVHK cells) were stimulated with epidermal growth factor (EGF) and ultraviolet B (UVB) irradiation. Following the stimulation, cell growth, apoptosis, and the activities of mitogen-activated protein (MAP) kinase families were analyzed. EGF (100 ng/ml) increased SVHK cell number c...
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abstract:BACKGROUND:Several inhibitor of apoptosis proteins (IAPs) are cleaved during apoptosis. Studies of the melanoma-associated IAP (ML-IAP) Livin, using recombinant molecules, have implicated both caspases 3/7 and the serine protease Omi/HtrA2 in its proteolytic cleavage. OBJECTIVE:To characterize the apoptotic cleavage o...
journal_title:Journal of dermatological science
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abstract:BACKGROUND:The capacity of photosensitizing chemicals with ultraviolet A light (UVA) to induce apoptosis is one of the methods to assess their phototoxic and potentially photoallergic properties, since apoptotic cells may be easily presented by antigen-presenting cells. OBJECTIVES:We examined the photoaggravated abili...
journal_title:Journal of dermatological science
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journal_title:Journal of dermatological science
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abstract:BACKGROUND:Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. OBJECTIVES:We assessed the photochemopreventive effect of several clinically used chemical peeling agents on the ultraviolet (UV)-irradiat...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2010.08.002
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journal_title:Journal of dermatological science
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Journal of dermatological science
pub_type: 杂志文章
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更新日期:2011-03-01 00:00:00
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journal_title:Journal of dermatological science
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doi:10.1016/j.jdermsci.2008.08.015
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更新日期:1997-05-01 00:00:00
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journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2009.03.005
更新日期:2009-07-01 00:00:00
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journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
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journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
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更新日期:2007-05-01 00:00:00
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journal_title:Journal of dermatological science
pub_type: 杂志文章
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更新日期:2020-11-01 00:00:00
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journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2013.07.002
更新日期:2013-11-01 00:00:00
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journal_title:Journal of dermatological science
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