Merkel Cell Polyomavirus Strains in Patients with Merkel Cell Carcinoma

Institut National de la Santé et de la Recherche Médicale, Unit 618, Tours, France.
Emerging Infectious Diseases (Impact Factor: 6.75). 07/2009; 15(6):960-2. DOI: 10.3201/eid1506.081463
Source: PubMed


We investigated whether Merkel cell carcinoma (MCC) patients in France carry Merkel cell polyomavirus (MCPyV) and then identified strain variations. All frozen MCC specimens and 45% of formalin-fixed and paraffin-embedded specimens, but none of the non-MCC neuroendocrine carcinomas specimens, had MCPyV. Strains from France and the United States were similar.

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    • "Reports using PCR to detect MCPyV in MCC vary in MCPyV positivity depending on primer pairs used ranging from 40% to 100% [Feng et al., 2008; Kassem et al., 2008; Becker et al., 2009; Busam et al., 2009; Duncavage et al., 2009; Garneski et al., 2009; Sastre- Garau et al., 2009; Shuda et al., 2009; Sihto et al., 2009; Touze et al., 2009; Varga et al., 2009; Wetzels et al., 2009; Bhatia et al., 2010; Houben et al., 2010; Loyo et al., 2010; Andres et al., 2011]. "
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    ABSTRACT: Merkel cell carcinoma is a highly malignant skin cancer which predominantly occurs in elderly and immunocompromised persons. The identification of the Merkel cell polyomavirus (MCPyV) has inaugurated a new understanding of Merkel cell carcinoma pathogenesis. The frequent detection of the virus in Merkel cell carcinoma tissue (70-90%), its monoclonal integration in the tumor cells and the expression of viral oncogenes highly suggest that MCPyV is causally linked to the pathogenesis of the majority of Merkel cell cancer (MCC) cases. Using qualitative and quantitative PCR together with immunohistochemical staining this study aimed at characterizing the presence of MCPyV sequences and viral early gene expression in a cohort of MCC cases (n = 32) selected in Northern Germany. 40-57% of the cases were identified as MCPyV positive with 40.6% of the cases positive by immunohistochemical staining and 51.6-57.6% positive by PCR. Interestingly, in the majority (64%) of LT-Antigen positive tumors only 25-50% of tumor cells express LT-Antigen. These data are in accord with published studies describing heterogeneity in MCPyV viral loads and suggest that detection of MCPyV in Merkel cell carcinoma by PCR should be undertaken using multiple primer pairs. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 10/2014; 86(10). DOI:10.1002/jmv.23808 · 2.35 Impact Factor
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    • "Thus, amino acid substitutions are likely to occur frequently in MCPyV. The same was also reported among French MCPyV isolates [14]. On the other hand, amino acid substitutions at other locations would contribute to the antigenic diversity of the Japanese MCPyV. "
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    ABSTRACT: Background Merkel cell polyomavirus (MCPyV) was identified originally in Merkel cell carcinoma (MCC), a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs) is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i) the major histological type of cervical cancer is the SCC; (ii) the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii) MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV). In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs) were also studied. Results Formalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR) and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19%) and 4/16 cervical ACs (25%) were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT)-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1)-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs. Conclusions This study provides the first observation that MCPyV coexists in a subset of HPV-associated cervical cancers from Japanese patients. The prevalence of MCPyV in these lesions was close to that observed in the cutaneous SCCs. Further worldwide epidemiological surveys are warranted to determine the possible association of MCPyV with pathogenesis of cervical cancers.
    Virology Journal 08/2012; 9(1):154. DOI:10.1186/1743-422X-9-154 · 2.18 Impact Factor
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    • "The sequences found in our CLL cases, designated CLL-JK, shared two nucleotide gaps at positions 774 and 775 with sequences from another Japanese isolate, TKS [GenBank: FJ464337] [19], and Asian isolate 16b [HM011548] [9], when compared with the sequence of North American isolate MCC350 [EU375803] (Figure 1). Touzé et al. [20] reported that the nucleotide sequences of French MCPyV isolates were different from the MCC350 isolate, but homologous to the Swedish isolate MKL-1 [FJ173815]. A recent study also showed that the nucleotide sequence of the Italian isolate B.C. shared 100 % homology with MKL-1 [18]. "
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    ABSTRACT: Chronic lymphocytic leukemia (CLL) is the rarest adult leukemia in Japan, whereas it is the most common leukemia in the Western world. Recent studies from the United States and Germany suggest a possible etiological association between Merkel cell polyomavirus (MCPyV) and CLL, although no data have been reported from Eastern countries. To increase the volume of relevant data, this study investigated the prevalence and DNA loads of MCPyV and human polyomavirus 9 (HPyV9), another lymphotropic polyomavirus, in Japanese CLL cases. We found that 9/27 CLL cases (33.3 %) were positive for MCPyV using quantitative real-time polymerase chain reaction analysis. The viral DNA loads ranged from 0.000017 to 0.0012 copies per cell. All cases were negative for HPyV9. One MCPyV-positive CLL case was evaluated by mutational analysis of the large T (LT) gene, which indicated the presence of wild-type MCPyV without a nucleotide deletion. DNA sequence analysis of the entire small T (ST) gene and the partial LT gene revealed that a Japanese MCPyV isolate, designated CLL-JK, had two nucleotide gaps when compared with the reference sequence of the North American isolate MCC350. This study provides the first evidence that MCPyV is present in a subset of Japanese CLL cases with low viral DNA loads. MCPyV and HPyV9 are unlikely to contribute directly to the development of CLL in the majority of Japanese cases. MCPyV isolated from the Japanese CLL cases may constitute an Asian group and its pathogenicity needs to be clarified in future studies.
    Journal of Hematology & Oncology 06/2012; 5(1):25. DOI:10.1186/1756-8722-5-25 · 4.81 Impact Factor
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