Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors

Shuda, Masahiro; Arora, Reety; Kwun, Hyun Jin; Feng, Huichen; Sarid, Ronit; Fernández‐Figueras, María‐Teresa; Tolstov, Yanis; Gjoerup, Ole; Mansukhani, Mahesh; Swerdlow, Steven H.; Chaudhary, Preet M.; Kirkwood, John M.; Nalesnik, Michael A.; Kant, Jeffrey A.; Weiss, Lawrence M.; Chang, Yuan

doi:10.1002/ijc.24510

Cited by 322 publications

(396 citation statements)

References 25 publications

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“…Hypothetically, immunosuppression related to CLL or its treatments might lead to MCPyV activation and subsequent genesis of MCC, and despite the reciprocal association between CLL and MCC, MCPyV might not have a major role in the molecular pathogenesis of CLL. In line with this, MCPyV DNA was recently found to be present only rarely and at low concentrations in human haematological malignancies (Shuda et al, 2009). The rates of MCPyV infection may also vary in different populations (Garneski et al, 2009), which may influence the frequency of MCC in patients diagnosed with CLL.…”

Section: Discussionmentioning

confidence: 81%

Chronic lymphocytic leukaemia patients have a high risk of Merkel-cell polyomavirus DNA-positive Merkel-cell carcinoma

et al. 2009

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BACKGROUND: Immunosuppression and Merkel-cell polyomavirus (MCPyV) infection may have a role in the pathogenesis of Merkelcell carcinoma (MCC), a rare neuroendocrine carcinoma of the skin. METHODS: We studied incidence of chronic lymphocytic leukaemia (CLL) and MCC from the files of the Finnish Cancer Registry and the largest hospital of Finland, Helsinki University Central Hospital, from 1979 to 2006. Presence of MCPyV DNA in MCCs was investigated by quantitative PCR. RESULTS: We identified 4164 patients diagnosed with CLL and 172 diagnosed with MCC. Six patients diagnosed with both diseases were found; CLL was the first diagnosis in four cases and MCC in two. The standardised incidence ratio (SIR) for CLL after the diagnosis of MCC was highly elevated, 17.9 (95% confidence interval (CI), 2.2 -64.6; Po0.001), and the SIR for MCC after the diagnosis of CLL was also elevated, 15.7 (3.2 -46.0, Po0.01). Merkel-cell polyomavirus DNA was present in all five MCCs with tumour tissue available for analysis. CONCLUSIONS: We conclude that patients diagnosed with CLL have a substantially increased risk for MCC, and vice versa. Merkel-cell polyomavirus DNA is frequently present in MCCs that occur in CLL patients. Immunosuppression related with CLL and viral infection might explain the association between CLL and MCC.

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Section: Discussionmentioning

confidence: 81%

Chronic lymphocytic leukaemia patients have a high risk of Merkel-cell polyomavirus DNA-positive Merkel-cell carcinoma

et al. 2009

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“…On the other hand, using the CM2B4 monoclonal antibody (91), MCPyV LTag is detected (Fig. 5) in the nuclei of 58-96% of MCCs (82,91,(97)(98)(99)(100)(101)(102)(103). According to these studies, immunodetection of LTag expression is found to be less sensitive but more specific than detection of MCPyV DNA by PCR.…”

Section: Histopathology and Detection Of Mcpyv Antigens In MCCmentioning

confidence: 92%

Human Merkel cell polyomavirus: virological background and clinical implications

Coursaget

Samimi

Nicol

et al. 2013

APMIS

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The Merkel cell polyomavirus (MCPyV), identified in humans in 2008, is associated with a relatively rare but aggressive neuroendocrine skin cancer, the Merkel cell carcinoma (MCC). MCC incidence is increasing due to the advancing age of the population, the increase in damaging sun exposure and in the number of immunocompromised individuals. MCPyV must be considered as the etiological agent of MCC and thus is the first example of a human oncogenic polyomavirus. MCPyV infection is common, and seroprevalence studies indicate that widespread exposure begins early in life. The majority of adults have anti-MCPyV antibodies and there is a growing body of evidence that healthy human skin harbors resident or transient MCPyV suggesting that MCPyV infection persists throughout life. However, the mode of transmission, the host cells, and the latency characteristics of this virus remain to be elucidated. In addition, it is still not clear whether MCPyV is associated with diseases or lesions other than Merkel cell carcinoma. The etiologic role of MCPyV in MCC opens up opportunities to improve the understanding of this cancer and to potentially improve its treatment.

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“…The most consistently detected region was at the 5′ end of LTAg exon 2 (also shared by ALTO and 57kT transcripts) (Supplementary Figure S2) (3,23,24), overlapping with a commonly targeted region for qPCR detection of MCPyV ( Figure 1). However, we and others have observed cases with high sTAg and low LTAg expression by qPCR (14,25).…”

Section: Nomination Of Rna-ish Probe Target Regionmentioning

confidence: 99%

Age and Gender Associations of Virus Positivity in Merkel Cell Carcinoma Characterized Using a Novel RNA In Situ Hybridization Assay

Wang

Harms

Palanisamy

et al. 2017

Clinical Cancer Research

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Purpose-Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine tumor of the skin. Merkel cell polyomavirus (MCPyV) plays an oncogenic role in the majority of MCCs. Detection of MCPyV in MCCs has diagnostic utility and prognostic potential. We investigated whether RNAscope, an RNA in situ hybridization (ISH) assay for detection of RNA transcripts in tissues, is useful for MCPyV detection.Experimental Design-We applied an RNAscope probe targeting MCPyV T antigen transcripts on tissue microarrays (TMAs) and whole tissue sections encompassing 87 MCCs from 75 patients, 14 carcinomas of other types, and benign tissues. For comparison, quantitative PCR (qPCR) was performed on 57 cases of MCC from 52 patients.Results-RNA-ISH demonstrated the presence of MCPyV in 37/75 (49.3%) cases. Notably, tumors from younger patients (< 73 years) had a significantly higher virus positivity than those from elderly patients (≥ 73 years) (64.9% vs. 34.2%, P =0.011). Female patients had a higher positive rate of MCPyV than male patients (66.7% vs. 39.6%, P =0.032). Data from both RNA- HHMI Author Manuscript HHMI Author Manuscript HHMI Author Manuscriptdetermining MCPyV status, RNAscope had 100% sensitivity and 100% specificity. There was a strong correlation between qPCR copy number and RNA-ISH product score (Spearman's correlation coefficient R 2 = 0.932, P < 0.0001).Conclusions-RNA-ISH is comparably sensitive to qPCR for detection of MCPyV and allows for correlation with tissue morphology. This study also reveals a significant association between age, gender, and MCPyV positivity.

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Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors

Cited by 322 publications

References 25 publications

Chronic lymphocytic leukaemia patients have a high risk of Merkel-cell polyomavirus DNA-positive Merkel-cell carcinoma

Chronic lymphocytic leukaemia patients have a high risk of Merkel-cell polyomavirus DNA-positive Merkel-cell carcinoma

Human Merkel cell polyomavirus: virological background and clinical implications

Age and Gender Associations of Virus Positivity in Merkel Cell Carcinoma Characterized Using a Novel RNA In Situ Hybridization Assay

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