Caracterização imunoistoquímica comparativa de subgrupos de células dendríticas e oncogênese viral no carcinoma espinocelular oral e orofaríngeo
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Data
2020-02-19
Autores
Silveira, Heitor Albergoni
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Universidade Estadual Paulista (Unesp)
Resumo
O carcinoma espinocelular (CEC) de cabeça e pescoço (CECCP) é o quinto tipo de câncer mais comum e a sexta causa de morte por câncer. Recentes estudos enfatizam o CEC oral (CECO) como uma entidade distinta do CEC de orofaringe (CECorof), com este último apresentando melhor prognóstico e estreitamente associado com infecção pelo papilomavírus humano (HPV). A etiologia do CECCP é multifatorial; porém, o CECO está relacionado com abuso do tabaco e álcool, enquanto o CECorof está frequentemente associado com infecção pelo HPV. As células dendríticas (CDs) são importantes células as quais regulam repostas imunes, incluindo aquelas vinculadas à tumorigênese, estabelecendo conexão entre o sistema imune inato e adaptativo. Estão divididas em dois grupos: CDs mieloides (CDmi) e CDs plasmocitóides (CDp), incluindo CDs imaturas (CDim) e CDs maduras (CDm). O objetivo do nosso estudo foi analisar comparativamente, através da técnica de imunoistoquímica (IQ) e hibridização in situ (HIS), a infiltração de CDmi e CDp, incluindo subgrupos de CDim e CDm, no CECO (n=109) e CECorof (n=126), bem como analisar a oncogênese viral (HPV amplo espectro, alto risco (ARHPV) e baixo risco (BRHPV) oncogênico e vírus Epstein-Barr [VEB]) por HIS. O CECOrof (25%) comparado com o CECO (11%) mostrou associação significativa com o HPV. No CECorof e no CECO, 19 e 7 mostram positividade para ARHPV (somente), 6 e 3 BRHPV (somente) e 3 e 2 ARHPV/BRHPV (co-infecção), respectivamente. Os tumores HPV-positivos comparados com os HPV-negativos apresentaram índice proliferativo significativamente maior através dos marcadores Ciclina D1 e Ki-67. O CECO associado ao ARHPV e ao BRHPV apresentou maior taxa de sobrevida global. No geral, os marcadores para imDC, foram significativamente mais frequentes no CECorof do que no CECO. Diferentemente, CECO e CECorof apresentaram maior número de marcadores de CDs submucosas (CDsub). Ambas as neoplasias apresentaram quantidades semelhantes de CDp ativadas. O grupo HPV+ mostrou um número maior de CDs em ambas as neoplasias do que o grupo HPV-. Vale ressaltar que um número significativamente maior de células CD207+ e CD123+ foi observado no CECorof HPV+ do que no CECO HPV+. Concluimos que diferente do CECO, nossos resultados mostram no CECorof predominância de CDim, com perfil de ativação de células imunes. A presença do HPV parece mostrar associação com a infiltração de CDs em ambas as neoplasias, sugerindo respostas imunes antivirais no CECorof HPV+.
Head and neck squamous cell carcinoma (SCC) (HNSCC) is the fifth most common type of cancer and the sixth leading cause of cancer death. Recent studies emphasize oral SCC (OSCC) as an entity distinct from oropharyngeal SCC (OPSCC), with the latter having a better prognosis and closely associated with human papillomavirus (HPV) infection. The etiology of HNSCC is multifactorial; however, OSCC is related to tobacco and alcohol abuse, while OPSCC is often associated with HPV infection. Dendritic cells (DCs) are important cells that regulate immune responses, including those linked to tumorigenesis, establishing a connection between the innate and adaptive immune systems. They are divided into two groups: myeloid DCs (myCD) and plasmacytoid DCs (pDC), including immature DCs (imDC) and mature CDs (mDC). The aim of our study was to comparatively analyze, through the immunohistochemistry (HIS) and in situ hybridization (ISH) technique, the infiltration of myCD and pDC, including subgroups of imDC and mDC, in the OSCC (n= 109) and OPSCC (n= 126), as well as analyzing viral oncogenesis (wide-spectrum HPV, high-risk (HRHPV) and low-risk (LRHPV) oncogenic and Epstein-Barr virus [EBV]) by ISH OPSCC (25%) compared to OSCC (11%) showed a significant association with HPV. In OPSCC and OSCC, 19 and 7 shows positivity for HRHPV (only), 6 and 3 LRHPV (only) and 3 and 2 HRHPV/LRHPV (co-infection), respectively. HPV-positive tumors compared to HPV-negative tumors showed a significantly higher proliferative index through the cyclin D1 and Ki-67 markers. The OSCC associated with HRHPV and LRHPV had the highest overall survival rate. Overall, markers for imDC were significantly more frequent in OPSCC than in OSCC. In contrast, OSCC and OPSCC had a higher number of subDC markers. Both neoplasms showed similar amounts of activated pCD. The HPV group showed a greater number of CDs in both neoplasms than the HPV-. It is noteworthy that a significantly higher number of CD207+ and CD123+ cells was observed in HPV-associated OPSCC than in HPV-associated OSCC. We concluded that unlike OSCC, our results show a predominance of imDCs, with an activation profile of immune cells, in OPSCC. The HPV status seems to show an association with the infiltration of DCs in both neoplasms, suggesting antiviral immune responses in the OPSCC associated with HPV. Keywords:
Head and neck squamous cell carcinoma (SCC) (HNSCC) is the fifth most common type of cancer and the sixth leading cause of cancer death. Recent studies emphasize oral SCC (OSCC) as an entity distinct from oropharyngeal SCC (OPSCC), with the latter having a better prognosis and closely associated with human papillomavirus (HPV) infection. The etiology of HNSCC is multifactorial; however, OSCC is related to tobacco and alcohol abuse, while OPSCC is often associated with HPV infection. Dendritic cells (DCs) are important cells that regulate immune responses, including those linked to tumorigenesis, establishing a connection between the innate and adaptive immune systems. They are divided into two groups: myeloid DCs (myCD) and plasmacytoid DCs (pDC), including immature DCs (imDC) and mature CDs (mDC). The aim of our study was to comparatively analyze, through the immunohistochemistry (HIS) and in situ hybridization (ISH) technique, the infiltration of myCD and pDC, including subgroups of imDC and mDC, in the OSCC (n= 109) and OPSCC (n= 126), as well as analyzing viral oncogenesis (wide-spectrum HPV, high-risk (HRHPV) and low-risk (LRHPV) oncogenic and Epstein-Barr virus [EBV]) by ISH OPSCC (25%) compared to OSCC (11%) showed a significant association with HPV. In OPSCC and OSCC, 19 and 7 shows positivity for HRHPV (only), 6 and 3 LRHPV (only) and 3 and 2 HRHPV/LRHPV (co-infection), respectively. HPV-positive tumors compared to HPV-negative tumors showed a significantly higher proliferative index through the cyclin D1 and Ki-67 markers. The OSCC associated with HRHPV and LRHPV had the highest overall survival rate. Overall, markers for imDC were significantly more frequent in OPSCC than in OSCC. In contrast, OSCC and OPSCC had a higher number of subDC markers. Both neoplasms showed similar amounts of activated pCD. The HPV group showed a greater number of CDs in both neoplasms than the HPV-. It is noteworthy that a significantly higher number of CD207+ and CD123+ cells was observed in HPV-associated OPSCC than in HPV-associated OSCC. We concluded that unlike OSCC, our results show a predominance of imDCs, with an activation profile of immune cells, in OPSCC. The HPV status seems to show an association with the infiltration of DCs in both neoplasms, suggesting antiviral immune responses in the OPSCC associated with HPV. Keywords:
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Palavras-chave
Carcinoma de células escamosas, Boca, Orofaringe, Papillomaviridae, Imuno-histoquímica, Células dendríticas, Squamous cell carcinoma, Papillomaviridae, Immunohistochemistry, Dendritic cells.