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The present authors&#8217; group was responsible for the first study in a Brazilian population&#44; with 32&#37; MCPyV positivity in biopsies of various NMSCs&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> The present study&#44; however&#44; focused on investigating MCPyV exclusively in basal cell carcinoma &#40;BCC&#41; patients&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A convenience sampling composed of fresh-frozen biopsies and perilesional skin was analyzed&#44; deriving from 35 consecutive patients with histopathological diagnosis of BCC treated at Ant&#244;nio Pedro University Hospital &#40;HUAP-UFF&#41; between September 2017 and December 2018&#46; Demographic data was collected during medical exam interview&#46; Ethnicity was defined by the dermatologist according to patient&#39;s phototype&#44; classified as &#8220;white&#8221; or &#8220;non-white&#46;&#8221; Tumor location was used to infer solar exposure &#40;high&#44; moderate&#44; or low&#41;&#46; All samples had DNA extracted utilizing a commercial kit according to manufacturer instructions&#46; MCPyV DNA was detected by nested polymerase chain reaction &#40;PCR&#41; for the LT3 region&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Statistical analysis was performed using SPSS v&#46; 20 software &#40;SPSS Inc&#46; &#8211; Chicago&#44; IL&#44; United States&#41;&#46; All individuals agreed to participate by signing an informed consent&#46; This study was approved by the University&#39;s Ethics Committee&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Eight of the 35 patients had more than one lesion&#46; In general&#44; patients were elderly &#40;72&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;8 years&#41;&#44; predominantly female &#40;62&#46;9&#37;&#41;&#44; white &#40;94&#46;3&#37;&#41;&#44; and immunocompetent &#40;97&#46;1&#37;&#41;&#46; The most common comorbidities found were systemic arterial hypertension &#40;68&#46;6&#37;&#41; and diabetes mellitus type 2 &#40;14&#46;3&#37;&#41;&#46; Eleven patients with previous history of neoplasia and three with premalignant lesions at the time of surgery were also identified&#46; The lesions were located mainly on the head &#40;68&#46;7&#37;&#41;&#44; neck &#40;14&#46;6&#37;&#41;&#44; upper limbs &#40;10&#46;4&#37;&#41;&#44; and lower limbs &#40;6&#46;3&#37;&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Patients were classified as MCPyV<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>if at least one lesion had detectable viral DNA&#44; resulting in nine &#40;25&#46;7&#37;&#41; MCPyV<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>patients&#46; In regard to surgical margins&#44; eight &#40;22&#46;8&#37;&#41; patients were MCPyV<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&#46; No statistically significant association &#40;<span class="elsevierStyleItalic">p</span>-value<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; was found between MCPyV positivity and the gender&#44; ethnicity&#44; age&#44; solar exposure&#44; and immune status of the patients&#46; The positivity for MCPyV when considering lesions &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41; and associated perilesional tissue was 45&#46;5&#37; and 54&#46;5&#37;&#44; respectively&#46; However&#44; the level of agreement between lesion <span class="elsevierStyleItalic">vs&#46;</span> associated perilesional tissue was considered low &#40;kappa<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;174&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; with ten &#40;28&#46;6&#37;&#41; patients showing disagreement for both samples&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">As a recently discovered epitheliotropic and oncogenic virus&#44; MCPyV became a sought-after research target in relation to NMSC samples&#46; Since the important risk factors and etiology of NMSC still lack comprehensive understanding&#44; this study aimed to evaluate MCPyV positivity in BCC&#44; the most prevalent type of NMSC&#44; in 35 patients&#46; The results showed that 25&#46;7&#37; of patients were MCPyV positive&#44; which is comparable with other studied populations&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">According to the results&#44; BCC lesions and perilesional skin presented similar detection rates for MCPyV detection&#44; which indicates that the virus is spread around the tissue regardless of the presence or absence of lesion&#44; as indicated by the low level of agreement for viral detection&#46; Whether MCPyV is incidental in this type of neoplasm or it plays a role in BCC development&#44; through DNA integration and inhibition of cellular regulatory pathways&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> is not yet known&#46; However&#44; it is hypothesized that oncoviruses may provide the initial favorable conditions for the development of neoplasia by the &#8220;hit and run&#8221; mechanism&#44; making it difficult to detect the agent once the lesion is established&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The lack of association between viral detection in BCC and immunological status&#44; age&#44; ethnicity&#44; and solar exposure indicate that they are not determinant of MCPyV in this type of neoplasm&#46; Regarding patients&#8217; comorbidities&#44; none showed significance for MCPyV positivity &#40;data not shown&#41;&#46; Unfortunately&#44; it was not possible to test these pre-malignant lesions for viral detection&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">From these findings MCPyV appears not to correlate with major risk factors for BCC development&#59; however&#44; this study expands the knowledge of MCPyV in the Brazilian population&#44; which is currently scarce&#46; Even with its high prevalence of mixed race&#44; the Brazilian population remains one of the most afflicted by NMSC worldwide and therefore all knowledge of possible risk factor associations is relevant to the country&#39;s public health&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0045" class="elsevierStylePara elsevierViewall">This study was funded by <span class="elsevierStyleGrantSponsor" id="gs1">FUNADERM</span> &#40;Fundo de Apoio &#224; Dermatologia&#41;&#46; This study was also partially funded by <span class="elsevierStyleGrantSponsor" id="gs2">FAPERJ</span> &#40;Funda&#231;&#227;o de Pesquisa do Rio de Janeiro&#41; and <span class="elsevierStyleGrantSponsor" id="gs3">Coordena&#231;&#227;o de Aperfei&#231;oamento de Pessoal de N&#237;vel Superior &#40;CAPES&#41;</span> &#8211; Financial Code 001&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#8217; contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">Marianna Tavares Venceslau Gon&#231;alves&#58; Drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Rafael Brandao Varella&#58; Statistical analysis&#59; approval of the final version of the manuscript&#59; conception and planning of the study&#59; 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Research Letter
Molecular detection of Merkel cell polyomavirus in basal cell carcinoma and perilesional tissue: a cross-sectional study
Marianna Tavares Venceslau Gonçalvesa, Rafael Brandão Varellab,
Autor para correspondência
rvarella@id.uff.br

Corresponding author.
, Núbia Karla de Oliveira Almeidac, Maria Angelica Arpon Marandino Guimarãesa, Flávio Barbosa Luzd
a Department of Preventive Medicine, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
b Department of Microbiology and Parasitology, Instituto Biomédico, Universidade Federal Fluminense, Rio de Janeiro, RJ, Brazil
c Department of Statistics, Universidade Federal Fluminense, Rio de Janeiro, RJ, Brazil
d Department of Dermatology, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ, Brazil
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The first and so far only oncogenic human polyomavirus&#44; Merkel cell polyomavirus &#40;MCPyV&#41;&#44; was discovered in the last decade&#44; infecting about 80&#37; of Merkel cell carcinomas &#40;MCC&#41;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> and 40&#37; of healthy individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Originated from cells located in the basal layer of the skin&#39;s epidermis&#44; MCC is a rare and extremely aggressive type of non-melanoma skin cancer &#40;NMSC&#41;&#44; which generally affects the elderly&#44; Caucasians and the immunocompromised in body areas with high UV exposure&#46; Comprising the most prevalent neoplasia worldwide&#44; NMSCs have been investigated to look for and elucidate other risk factors&#44; such as infections by oncoviruses&#46; The present authors&#8217; group was responsible for the first study in a Brazilian population&#44; with 32&#37; MCPyV positivity in biopsies of various NMSCs&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> The present study&#44; however&#44; focused on investigating MCPyV exclusively in basal cell carcinoma &#40;BCC&#41; patients&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A convenience sampling composed of fresh-frozen biopsies and perilesional skin was analyzed&#44; deriving from 35 consecutive patients with histopathological diagnosis of BCC treated at Ant&#244;nio Pedro University Hospital &#40;HUAP-UFF&#41; between September 2017 and December 2018&#46; Demographic data was collected during medical exam interview&#46; Ethnicity was defined by the dermatologist according to patient&#39;s phototype&#44; classified as &#8220;white&#8221; or &#8220;non-white&#46;&#8221; Tumor location was used to infer solar exposure &#40;high&#44; moderate&#44; or low&#41;&#46; All samples had DNA extracted utilizing a commercial kit according to manufacturer instructions&#46; MCPyV DNA was detected by nested polymerase chain reaction &#40;PCR&#41; for the LT3 region&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Statistical analysis was performed using SPSS v&#46; 20 software &#40;SPSS Inc&#46; &#8211; Chicago&#44; IL&#44; United States&#41;&#46; All individuals agreed to participate by signing an informed consent&#46; This study was approved by the University&#39;s Ethics Committee&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Eight of the 35 patients had more than one lesion&#46; In general&#44; patients were elderly &#40;72&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;8 years&#41;&#44; predominantly female &#40;62&#46;9&#37;&#41;&#44; white &#40;94&#46;3&#37;&#41;&#44; and immunocompetent &#40;97&#46;1&#37;&#41;&#46; The most common comorbidities found were systemic arterial hypertension &#40;68&#46;6&#37;&#41; and diabetes mellitus type 2 &#40;14&#46;3&#37;&#41;&#46; Eleven patients with previous history of neoplasia and three with premalignant lesions at the time of surgery were also identified&#46; The lesions were located mainly on the head &#40;68&#46;7&#37;&#41;&#44; neck &#40;14&#46;6&#37;&#41;&#44; upper limbs &#40;10&#46;4&#37;&#41;&#44; and lower limbs &#40;6&#46;3&#37;&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Patients were classified as MCPyV<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>if at least one lesion had detectable viral DNA&#44; resulting in nine &#40;25&#46;7&#37;&#41; MCPyV<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>patients&#46; In regard to surgical margins&#44; eight &#40;22&#46;8&#37;&#41; patients were MCPyV<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&#46; No statistically significant association &#40;<span class="elsevierStyleItalic">p</span>-value<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; was found between MCPyV positivity and the gender&#44; ethnicity&#44; age&#44; solar exposure&#44; and immune status of the patients&#46; The positivity for MCPyV when considering lesions &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41; and associated perilesional tissue was 45&#46;5&#37; and 54&#46;5&#37;&#44; respectively&#46; However&#44; the level of agreement between lesion <span class="elsevierStyleItalic">vs&#46;</span> associated perilesional tissue was considered low &#40;kappa<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;174&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; with ten &#40;28&#46;6&#37;&#41; patients showing disagreement for both samples&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">As a recently discovered epitheliotropic and oncogenic virus&#44; MCPyV became a sought-after research target in relation to NMSC samples&#46; Since the important risk factors and etiology of NMSC still lack comprehensive understanding&#44; this study aimed to evaluate MCPyV positivity in BCC&#44; the most prevalent type of NMSC&#44; in 35 patients&#46; The results showed that 25&#46;7&#37; of patients were MCPyV positive&#44; which is comparable with other studied populations&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">According to the results&#44; BCC lesions and perilesional skin presented similar detection rates for MCPyV detection&#44; which indicates that the virus is spread around the tissue regardless of the presence or absence of lesion&#44; as indicated by the low level of agreement for viral detection&#46; Whether MCPyV is incidental in this type of neoplasm or it plays a role in BCC development&#44; through DNA integration and inhibition of cellular regulatory pathways&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> is not yet known&#46; However&#44; it is hypothesized that oncoviruses may provide the initial favorable conditions for the development of neoplasia by the &#8220;hit and run&#8221; mechanism&#44; making it difficult to detect the agent once the lesion is established&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The lack of association between viral detection in BCC and immunological status&#44; age&#44; ethnicity&#44; and solar exposure indicate that they are not determinant of MCPyV in this type of neoplasm&#46; Regarding patients&#8217; comorbidities&#44; none showed significance for MCPyV positivity &#40;data not shown&#41;&#46; Unfortunately&#44; it was not possible to test these pre-malignant lesions for viral detection&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">From these findings MCPyV appears not to correlate with major risk factors for BCC development&#59; however&#44; this study expands the knowledge of MCPyV in the Brazilian population&#44; which is currently scarce&#46; Even with its high prevalence of mixed race&#44; the Brazilian population remains one of the most afflicted by NMSC worldwide and therefore all knowledge of possible risk factor associations is relevant to the country&#39;s public health&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0045" class="elsevierStylePara elsevierViewall">This study was funded by <span class="elsevierStyleGrantSponsor" id="gs1">FUNADERM</span> &#40;Fundo de Apoio &#224; Dermatologia&#41;&#46; This study was also partially funded by <span class="elsevierStyleGrantSponsor" id="gs2">FAPERJ</span> &#40;Funda&#231;&#227;o de Pesquisa do Rio de Janeiro&#41; and <span class="elsevierStyleGrantSponsor" id="gs3">Coordena&#231;&#227;o de Aperfei&#231;oamento de Pessoal de N&#237;vel Superior &#40;CAPES&#41;</span> &#8211; Financial Code 001&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#8217; contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">Marianna Tavares Venceslau Gon&#231;alves&#58; Drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Rafael Brandao Varella&#58; Statistical analysis&#59; approval of the final version of the manuscript&#59; conception and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; participation in design of the study&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">N&#250;bia Karla de Oliveira Almeida&#58; Collection&#44; analysis&#44; and interpretation of data&#59; critical review of the literature&#44; critical review of the manuscript&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Maria Angelica Arpon Marandino Guimar&#227;es&#58; Drafting and editing of the manuscript&#59; participation in design of the study&#59; critical review of the manuscript&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Fl&#225;vio Barbosa Luz&#58; Approval of final version of the manuscript&#59; conception and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; participation in design of the study&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the manuscript&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#43;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t">0&#46;174 &#40;&#8722;0&#46;128 to 0&#46;476&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                      "titulo" => "Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin"
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ISSN: 03650596
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