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moderada ou grave de acordo com os crit&#233;rios morfol&#243;gicos da Organiza&#231;&#227;o Mundial da Sa&#250;de &#40;OMS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Para a an&#225;lise imuno&#8208;histoqu&#237;mica&#44; o material tratado com o anticorpo anti&#8208;8&#8208;OHdG &#40;Santa Cruz Biotechnology Cat&#35; sc&#8208;66036&#44; RRID&#58; AB 832272&#41; foi examinado por dois avaliadores previamente calibrados e cegados&#46; A an&#225;lise foi realizada por microscopia &#243;ptica nos aumentos de 100&#215; e 400&#215; no componente epitelial em toda a les&#227;o&#44; cuja extens&#227;o foi determinada pela &#225;rea de elastose solar no tecido conjuntivo e por altera&#231;&#245;es epiteliais&#44; se presentes&#46; Os casos foram categorizados com base em escore de imunorreatividade&#46; Para esse prop&#243;sito&#44; a intensidade da colora&#231;&#227;o foi avaliada primeiramente no epit&#233;lio e classificada da seguinte maneira&#58; 0 &#40;negativa&#41;&#44; 1 &#40;fraca&#41;&#44; 2 &#40;moderada&#41; e 3 &#40;forte&#41;&#46; Foi considerada a intensidade predominante em cada caso&#46; A imunomarca&#231;&#227;o foi analisada semiquantitativamente&#44; atribuindo&#8208;se os seguintes escores&#58; 0 &#40;negativo&#41;&#44; 1 &#40;1&#37; a 50&#37; de c&#233;lulas positivas&#41; e 2 &#40;51&#37; a 100&#37; de c&#233;lulas positivas&#41;&#46; As c&#233;lulas epiteliais que exibiam colora&#231;&#227;o marrom no n&#250;cleo e&#47;ou citoplasma foram classificadas como positivas&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;7</span></a> O escore de imunorreatividade foi ent&#227;o calculado multiplicando&#8208;se o escore de intensidade da colora&#231;&#227;o pelo escore da porcentagem de c&#233;lulas positivas&#46; O escore final de cada caso variou de 0 a 6&#44; em que 0&#8208;2 &#61; imunorreatividade fraca&#44; 3&#8208;4 &#61; imunorreatividade moderada e 5&#8208;6<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>imunorreatividade forte&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Houve predom&#237;nio de pacientes do sexo masculino &#40;72&#44;2&#37;&#41; e brancos &#40;64&#44;9&#37;&#41;&#44; n&#227;o fumantes ou ex&#8208;fumantes &#40;49&#44;2&#37;&#41;&#44; com idade igual ou superior a 40 anos &#40;93&#37;&#41; e com hist&#243;ria de exposi&#231;&#227;o cr&#244;nica &#224; radia&#231;&#227;o ultravioleta &#40;66&#44;7&#37;&#41;&#46; Manchas brancas foram a caracter&#237;stica cl&#237;nica mais frequente nos casos estudados &#40;56&#44;1&#37;&#41;&#44; seguidas de placa branca e descama&#231;&#227;o&#59; ulcera&#231;&#227;o foi menos comum &#40;10&#44;5&#37;&#59; <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Imunomarca&#231;&#227;o nas c&#233;lulas epiteliais foi observada em 100&#37; dos casos analisados&#44; principalmente nas camadas basal e parabasal do epit&#233;lio&#46; A imunomarca&#231;&#227;o foi predominantemente nuclear com colora&#231;&#227;o citoplasm&#225;tica de pequena intensidade em 39&#44;6&#37; dos casos e colora&#231;&#227;o predominantemente citoplasm&#225;tica em 12&#44;1&#37;&#44; enquanto a mesma intensidade foi observada no n&#250;cleo e citoplasma de 48&#44;3&#37; dos casos&#46; Forte imunorreatividade ao anticorpo foi detectada em 64&#44;9&#37; dos casos &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; A imunomarca&#231;&#227;o no n&#250;cleo e no citoplasma pode ser explicada pelo fato de que 8&#8208;OHdG &#233; encontrada tanto no DNA nuclear quanto no mitocondrial&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">O estresse oxidativo no DNA estava presente independentemente das caracter&#237;sticas cl&#237;nicas das les&#245;es&#46; N&#227;o foram encontradas diferen&#231;as estatisticamente significantes na express&#227;o de 8&#8208;OHdG de acordo com as caracter&#237;sticas cl&#237;nicas das les&#245;es &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#59; <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41; ou presen&#231;a de tabagismo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;266&#59; <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; Prabhulkar e Li monitoraram a cin&#233;tica de libera&#231;&#227;o de 8&#8208;OhdG na superf&#237;cie de uma c&#233;lula epitelial pulmonar exposta &#224; nicotina para avaliar o dano oxidativo causado pelo tabaco&#59; os autores observaram que quanto maior o n&#237;vel de exposi&#231;&#227;o celular &#224; nicotina&#44; maior o dano oxidativo ao DNA&#44; promovendo aumento no n&#237;vel de 8&#8208;OhdG secretada pela c&#233;lula&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Nas amostras do presente estudo&#44; foram observados danos oxidativos ao DNA demonstrados pela presen&#231;a de 8&#8208;OhdG&#44; independentemente da exposi&#231;&#227;o dos indiv&#237;duos ao tabaco&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">A classifica&#231;&#227;o histopatol&#243;gica revelou algum grau de displasia epitelial em 87&#44;7&#37; dos casos&#46; Displasia epitelial de pequeno grau foi a mais comum &#40;38&#44;6&#37;&#41;&#44; seguida pela displasia epitelial moderada &#40;29&#44;8&#37;&#41; e acentuada &#40;19&#44;3&#37;&#41;&#46; Displasia epitelial esteve ausente em 12&#44;3&#37; dos casos&#46; Forte imunorreatividade foi observada na maioria dos casos&#44; independentemente da presen&#231;a de displasia epitelial ou de seu grau&#46; N&#227;o foi observada diferen&#231;a significante na express&#227;o de 8&#8208;OhdG entre os diferentes graus de displasia epitelial oral &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;225&#59; <a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46; De maneira similar&#44; Yoshifuku et al&#46; tamb&#233;m encontraram predomin&#226;ncia de forte imunorreatividade com 8OHdG em les&#245;es de ceratose act&#237;nica &#40;presen&#231;a de displasia epitelial de pequeno grau ou moderada&#41; e doen&#231;a de Bowen &#40;displasia epitelial acentuada&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Esses achados podem ser explicados pelo fato de que a exposi&#231;&#227;o cr&#244;nica &#224; radia&#231;&#227;o ultravioleta desencadeia a produ&#231;&#227;o cont&#237;nua de esp&#233;cies reativas de oxig&#234;nio e estresse oxidativo e&#44; consequentemente&#44; a forma&#231;&#227;o constante de 8&#8208;OHdG&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Embora a express&#227;o de 8&#8208;OHdG seja &#250;til para a avalia&#231;&#227;o do dano oxidativo ao DNA e esteja bem estabelecida como indicador progn&#243;stico em diferentes tipos de c&#226;ncer&#44; com evid&#234;ncias sugerindo que o dano oxidativo ao DNA por meio da forma&#231;&#227;o de 8&#8208;OHdG est&#225; envolvido na patog&#234;nese e progress&#227;o do carcinoma espinocelular&#44;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7&#44;8&#44;10</span></a> os presentes resultados apontam para dificuldades na utiliza&#231;&#227;o desse marcador para estabelecer associa&#231;&#227;o com caracter&#237;sticas clinicodemogr&#225;ficas e com o grau morfol&#243;gico da queilite act&#237;nica&#44; uma vez que a 8&#8208;OHdG foi expressa de modo marcante na maioria dos casos analisados&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Os resultados do presente estudo confirmam que o estresse oxidativo por danos ao DNA desempenha papel na queilite act&#237;nica&#44; como sugerido pela forte express&#227;o imuno&#8208;histoqu&#237;mica de 8&#8208;OHdG nos casos analisados&#46; Entretanto&#44; a falta de diferen&#231;a significante na imunorreatividade anti&#8208;8&#8208;OHdG entre diferentes graus de displasia epitelial oral e fatores clinicodemogr&#225;ficos demonstra que esse marcador est&#225; alterado independentemente das caracter&#237;sticas cl&#237;nicas e do grau de displasia epitelial&#44; e as modifica&#231;&#245;es oxidativas da base do DNA s&#227;o um evento inicial na carcinog&#234;nese labial&#46; Assim&#44; tratamentos medicamentosos adjuvantes que minimizem os danos causados pelo estresse oxidativo&#44; como agentes antioxidantes t&#243;picos&#44; podem ser medidas terap&#234;uticas &#250;teis em pacientes com queilite act&#237;nica&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Suporte financeiro</span><p id="par0055" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Contribui&#231;&#227;o dos autores</span><p id="par0060" class="elsevierStylePara elsevierViewall">C&#237;ntia Barreto de Oliveira Varela&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; revis&#227;o cr&#237;tica da literatura&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Cristianne Kalinne Santos Medeiros&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; an&#225;lise estat&#237;stica&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Jabes Gennedyr da Cruz Lima&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">&#201;ricka Janine Dantas da Silveira&#58; Concep&#231;&#227;o e planejamento do estudo&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Patr&#237;cia Teixeira de Oliveira&#58; Concep&#231;&#227;o e planejamento do estudo&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflito de interesses</span><p id="par0085" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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          "pt" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Perfil de express&#227;o de 8&#8208;OHdG na queilite act&#237;nica &#40;QA&#41;&#46; &#40;A&#41; Escore de imunorreatividade 1 em QA sem displasia epitelial &#40;100&#215;&#41;&#46; &#40;B&#41; Escore de imunorreatividade 2 em QA com displasia epitelial de pequeno grau&#46; Notar o predom&#237;nio da imunomarca&#231;&#227;o nuclear &#40;200&#215;&#41;&#46; &#40;C&#41; Escore de imunorreatividade 3 em QA com displasia epitelial moderada&#46; Notar o predom&#237;nio da imunomarca&#231;&#227;o nuclear &#40;200&#215;&#41;&#46; &#40;D&#41; Escore de imunorreatividade 3 em QA com displasia epitelial moderada&#46; Notar o predom&#237;nio de colora&#231;&#227;o citoplasm&#225;tica &#40;200&#215;&#41;&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Branca&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">37&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fumante&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">89&#44;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Imunorreatividade da 8&#8208;OHdG</th></tr><tr title="table-row"><th class="td" title="\n
                  \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">n&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mediana&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Q25&#8208;Q75&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Descama&#231;&#227;o</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;00&#8208;3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;00&#8208;3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "pt" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Tamanho amostral&#44; mediana&#44; 25&#176; e 75&#176; quartis e signific&#226;ncia estat&#237;stica &#40;p&#41; para escore de imunorreatividade da 8&#8208;OHdG de acordo com as caracter&#237;sticas cl&#237;nicas da queilite act&#237;nica</p>"
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                0 => """
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vari&#225;vel</th><th class="td" title="\n
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                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Imunorreatividade da 8&#8208;OHdG</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mediana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Q25&#8208;Q75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Fumante&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#44;00&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#44;00&#8208;3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">N&#227;o fumante&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;00&#8208;3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;266&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Ex&#8208;fumante&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#44;50&#8208;3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&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  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Q25&#8208;Q75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Sem displasia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;00&#8208;3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Displasia epitelial de pequeno grau&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#44;00&#8208;3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;225&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Displasia epitelial moderada&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;00&#8208;3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Displasia epitelial acentuada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#44;50&#8208;3&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab3523000.png"
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Tamanho amostral&#44; mediana&#44; 25&#176; e 75&#176; quartis e signific&#226;ncia estat&#237;stica &#40;p&#41; para escore de imunorreatividade da 8&#8208;OHdG de acordo com a classifica&#231;&#227;o da OMS para displasia epitelial oral</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:10 [
            0 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical features and presentation of oral potentially malignant disorders"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46; Warnakulasuriya"
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                        ]
                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.oooo.2018.03.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Oral Surg Oral Med Oral Pathol Oral Radiol&#46;"
                        "fecha" => "2018"
                        "volumen" => "125"
                        "paginaInicial" => "582"
                        "paginaFinal" => "590"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29673799"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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            1 => array:3 [
              "identificador" => "bib0060"
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                0 => array:2 [
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Journal Information
Vol. 99. Issue 3.
Pages 433-436 (1 May 2024)
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3360
Vol. 99. Issue 3.
Pages 433-436 (1 May 2024)
Cartas ‐ Investigação
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A imunoexpressão da proteína 8‐hidroxi‐2’‐desoxiguanosina está associada à patogênese da queilite actínica
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Cíntia Barreto de Oliveira Varela, Cristianne Kalinne Santos Medeiros
Corresponding author
cristiannekalinne@gmail.com

Autor para correspondência.
, Jabes Gennedyr da Cruz Lima, Éricka Janine Dantas da Silveira, Patrícia Teixeira de Oliveira
Programa de Pós‐Graduação em Ciências Odontológicas, Departamento de Odontologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil
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Tabela 1. Distribuição amostral de acordo com os dados demográficos e características clínicas da queilite actínica
Tabela 2. Tamanho amostral, mediana, 25° e 75° quartis e significância estatística (p) para escore de imunorreatividade da 8‐OHdG de acordo com as características clínicas da queilite actínica
Tabela 3. Tamanho amostral, mediana, 25° e 75° quartis e significância estatística (p) para o escore final de imunorreatividade da 8‐OHdG de acordo com o tabagismo
Tabela 4. Tamanho amostral, mediana, 25° e 75° quartis e significância estatística (p) para escore de imunorreatividade da 8‐OHdG de acordo com a classificação da OMS para displasia epitelial oral
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Prezado Editor,

A queilite actínica (QA) é condição inflamatória crônica potencialmente maligna que pode progredir para carcinoma espinocelular do lábio. A radiação ultravioleta é o principal fator associado ao desenvolvimento da QA.1‐3 A exposição crônica à radiação ultravioleta leva à geração de espécies reativas de oxigênio que podem causar modificações oxidativas nas bases do DNA, principalmente na guanina, gerando 8‐hidroxi‐2’‐desoxiguanosina (8‐OHdG), que pode desencadear mutações genéticas e, portanto, tem sido utilizada como marcador sensível de dano oxidativo e como fator prognóstico para câncer de pele, de pulmão, de esôfago, de mama, de cólon e linfoma, entre outros.4,5

Trata‐se de estudo retrospectivo, descritivo e semiquantitativo da expressão imuno‐histoquímica da proteína 8‐OHdG no epitélio de revestimento de 57 amostras de QA. O estudo foi aprovado pelo Comitê de Ética da Universidade Federal do Rio Grande do Norte (Protocolo n° 3.476.834).

Para o estudo morfológico, foram obtidos cortes de 5μm do material emblocado em parafina, montados em lâminas de vidro e corados pelo método da hematoxilina & eosina. Os cortes histológicos foram examinados e classificados como sem ou com displasia epitelial que foi graduada como displasia leve, moderada ou grave de acordo com os critérios morfológicos da Organização Mundial da Saúde (OMS).6

Para a análise imuno‐histoquímica, o material tratado com o anticorpo anti‐8‐OHdG (Santa Cruz Biotechnology Cat# sc‐66036, RRID: AB 832272) foi examinado por dois avaliadores previamente calibrados e cegados. A análise foi realizada por microscopia óptica nos aumentos de 100× e 400× no componente epitelial em toda a lesão, cuja extensão foi determinada pela área de elastose solar no tecido conjuntivo e por alterações epiteliais, se presentes. Os casos foram categorizados com base em escore de imunorreatividade. Para esse propósito, a intensidade da coloração foi avaliada primeiramente no epitélio e classificada da seguinte maneira: 0 (negativa), 1 (fraca), 2 (moderada) e 3 (forte). Foi considerada a intensidade predominante em cada caso. A imunomarcação foi analisada semiquantitativamente, atribuindo‐se os seguintes escores: 0 (negativo), 1 (1% a 50% de células positivas) e 2 (51% a 100% de células positivas). As células epiteliais que exibiam coloração marrom no núcleo e/ou citoplasma foram classificadas como positivas.5,7 O escore de imunorreatividade foi então calculado multiplicando‐se o escore de intensidade da coloração pelo escore da porcentagem de células positivas. O escore final de cada caso variou de 0 a 6, em que 0‐2 = imunorreatividade fraca, 3‐4 = imunorreatividade moderada e 5‐6=imunorreatividade forte.

Houve predomínio de pacientes do sexo masculino (72,2%) e brancos (64,9%), não fumantes ou ex‐fumantes (49,2%), com idade igual ou superior a 40 anos (93%) e com história de exposição crônica à radiação ultravioleta (66,7%). Manchas brancas foram a característica clínica mais frequente nos casos estudados (56,1%), seguidas de placa branca e descamação; ulceração foi menos comum (10,5%; tabela 1).

Tabela 1.

Distribuição amostral de acordo com os dados demográficos e características clínicas da queilite actínica

 
Gênero     
Masculino  44  72,2 
Feminino  13  22,8 
Idade (anos)     
<40  7,0 
≥ 40  53  93,0 
Etniaa     
Branca  37  64,9 
Negra  15  26,3 
Tabagismoa     
Não fumante  11  19,3 
Fumante  7,0 
Ex‐fumante  17  29,8 
Descamação     
Sim  27  47,4 
Não  30  52,6 
Mancha branca     
Sim  32  56,1 
Não  25  43,9 
Placa branca     
Sim  28  49,1 
Não  29  50,9 
Eritema     
Sim  25  43,9 
Não  32  56,1 
Úlcera     
Sim  10,5 
Não  51  89,5 
a

Dados perdidos: etnia ‐ 5 (8,8%) casos; tabagismo ‐ 25 (43,9%) casos.

Imunomarcação nas células epiteliais foi observada em 100% dos casos analisados, principalmente nas camadas basal e parabasal do epitélio. A imunomarcação foi predominantemente nuclear com coloração citoplasmática de pequena intensidade em 39,6% dos casos e coloração predominantemente citoplasmática em 12,1%, enquanto a mesma intensidade foi observada no núcleo e citoplasma de 48,3% dos casos. Forte imunorreatividade ao anticorpo foi detectada em 64,9% dos casos (fig. 1). A imunomarcação no núcleo e no citoplasma pode ser explicada pelo fato de que 8‐OHdG é encontrada tanto no DNA nuclear quanto no mitocondrial.8,9

Figura 1.

Perfil de expressão de 8‐OHdG na queilite actínica (QA). (A) Escore de imunorreatividade 1 em QA sem displasia epitelial (100×). (B) Escore de imunorreatividade 2 em QA com displasia epitelial de pequeno grau. Notar o predomínio da imunomarcação nuclear (200×). (C) Escore de imunorreatividade 3 em QA com displasia epitelial moderada. Notar o predomínio da imunomarcação nuclear (200×). (D) Escore de imunorreatividade 3 em QA com displasia epitelial moderada. Notar o predomínio de coloração citoplasmática (200×).

(0.97MB).

O estresse oxidativo no DNA estava presente independentemente das características clínicas das lesões. Não foram encontradas diferenças estatisticamente significantes na expressão de 8‐OHdG de acordo com as características clínicas das lesões (p>0,05; tabela 2) ou presença de tabagismo (p=0,266; tabela 3). Prabhulkar e Li monitoraram a cinética de liberação de 8‐OhdG na superfície de uma célula epitelial pulmonar exposta à nicotina para avaliar o dano oxidativo causado pelo tabaco; os autores observaram que quanto maior o nível de exposição celular à nicotina, maior o dano oxidativo ao DNA, promovendo aumento no nível de 8‐OhdG secretada pela célula.8 Nas amostras do presente estudo, foram observados danos oxidativos ao DNA demonstrados pela presença de 8‐OhdG, independentemente da exposição dos indivíduos ao tabaco.

Tabela 2.

Tamanho amostral, mediana, 25° e 75° quartis e significância estatística (p) para escore de imunorreatividade da 8‐OHdG de acordo com as características clínicas da queilite actínica

VariávelImunorreatividade da 8‐OHdG
Mediana  Q25‐Q75 
Descamação        0,741 
Sim  27  3,00  2,00‐3,00   
Não  30  3,00  1,75‐3,00   
Mancha branca        0,506 
Sim  32  3,00  2,00‐3,00   
Não  25  3,00  1,50‐3,00   
Placa branca        0,479 
Sim  28  3,00  1,25‐3,00   
Não  29  3,00  2,00‐3,00   
Eritema        0,087 
Sim  25  3,00  1,00‐3,00   
Não  32  3,00  2,25‐3,00   
Úlcera        0,065 
Sim  1,50  1,00‐3,00   
Não  51  3,00  2,00‐3,00   

Teste de Mann‐Whitney.

Tabela 3.

Tamanho amostral, mediana, 25° e 75° quartis e significância estatística (p) para o escore final de imunorreatividade da 8‐OHdG de acordo com o tabagismo

VariávelImunorreatividade da 8‐OHdG
Mediana  Q25‐Q75 
Fumante  3,00  3,00‐3,00   
Não fumante  11  3,00  1,00‐3,00  0,266 
Ex‐fumante  17  3,00  1,50‐3,00   

Teste de Kruskal‐Wallis.

A classificação histopatológica revelou algum grau de displasia epitelial em 87,7% dos casos. Displasia epitelial de pequeno grau foi a mais comum (38,6%), seguida pela displasia epitelial moderada (29,8%) e acentuada (19,3%). Displasia epitelial esteve ausente em 12,3% dos casos. Forte imunorreatividade foi observada na maioria dos casos, independentemente da presença de displasia epitelial ou de seu grau. Não foi observada diferença significante na expressão de 8‐OhdG entre os diferentes graus de displasia epitelial oral (p=0,225; tabela 4). De maneira similar, Yoshifuku et al. também encontraram predominância de forte imunorreatividade com 8OHdG em lesões de ceratose actínica (presença de displasia epitelial de pequeno grau ou moderada) e doença de Bowen (displasia epitelial acentuada).5 Esses achados podem ser explicados pelo fato de que a exposição crônica à radiação ultravioleta desencadeia a produção contínua de espécies reativas de oxigênio e estresse oxidativo e, consequentemente, a formação constante de 8‐OHdG.

Tabela 4.

Tamanho amostral, mediana, 25° e 75° quartis e significância estatística (p) para escore de imunorreatividade da 8‐OHdG de acordo com a classificação da OMS para displasia epitelial oral

Classificação da OMSImunorreatividade da 8‐OHdG
Mediana  Q25‐Q75 
Sem displasia  3,00  3,00‐3,00   
Displasia epitelial de pequeno grau  22  3,00  2,00‐3,00  0,225 
Displasia epitelial moderada  17  3,00  3,00‐3,00   
Displasia epitelial acentuada  11  3,00  2,50‐3,00   

Teste de Kruskal‐Wallis.

Embora a expressão de 8‐OHdG seja útil para a avaliação do dano oxidativo ao DNA e esteja bem estabelecida como indicador prognóstico em diferentes tipos de câncer, com evidências sugerindo que o dano oxidativo ao DNA por meio da formação de 8‐OHdG está envolvido na patogênese e progressão do carcinoma espinocelular,7,8,10 os presentes resultados apontam para dificuldades na utilização desse marcador para estabelecer associação com características clinicodemográficas e com o grau morfológico da queilite actínica, uma vez que a 8‐OHdG foi expressa de modo marcante na maioria dos casos analisados.

Os resultados do presente estudo confirmam que o estresse oxidativo por danos ao DNA desempenha papel na queilite actínica, como sugerido pela forte expressão imuno‐histoquímica de 8‐OHdG nos casos analisados. Entretanto, a falta de diferença significante na imunorreatividade anti‐8‐OHdG entre diferentes graus de displasia epitelial oral e fatores clinicodemográficos demonstra que esse marcador está alterado independentemente das características clínicas e do grau de displasia epitelial, e as modificações oxidativas da base do DNA são um evento inicial na carcinogênese labial. Assim, tratamentos medicamentosos adjuvantes que minimizem os danos causados pelo estresse oxidativo, como agentes antioxidantes tópicos, podem ser medidas terapêuticas úteis em pacientes com queilite actínica.

Suporte financeiro

Nenhum.

Contribuição dos autores

Cíntia Barreto de Oliveira Varela: Obtenção, análise e interpretação dos dados; revisão crítica da literatura; elaboração e redação do manuscrito; aprovação da versão final do manuscrito.

Cristianne Kalinne Santos Medeiros: Obtenção, análise e interpretação dos dados; análise estatística; aprovação da versão final do manuscrito.

Jabes Gennedyr da Cruz Lima: Obtenção, análise e interpretação dos dados; aprovação da versão final do manuscrito.

Éricka Janine Dantas da Silveira: Concepção e planejamento do estudo; participação efetiva na orientação da pesquisa; aprovação da versão final do manuscrito.

Patrícia Teixeira de Oliveira: Concepção e planejamento do estudo; participação efetiva na orientação da pesquisa; aprovação da versão final do manuscrito.

Conflito de interesses

Nenhum.

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Como citar este artigo: Varela CBO, Medeiros CKS, Lima JGC, Da Silveira EJD, Oliveira PT. 8‐Hydroxy‐2’‐deoxyguanosine protein immunoexpression is associated with the pathogenesis of actinic cheilitis. An Bras Dermatol. 2024;99:433–6.

Trabalho realizado no Departamento de Odontologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.

Copyright © 2024. Sociedade Brasileira de Dermatologia
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