Influência da imunoexpressão das proteínas do sistema Mismatch repair na progressão tumoral e no prognóstico de pacientes com câncer de orofaringe

• Autor(a) principal: Oliveira Filho, Osias Vieira de
• Data de Publicação: 2021
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
• Texto Completo: http://www.repositorio.ufc.br/handle/riufc/56586
• topic: Neoplasias Orofaríngeas; Proteína MutS de Ligação de DNA com Erro de Pareamento; Proteínas MutL; Análise de Sobrevida

Cases of oropharyngeal squamous cell carcinoma are on the rise and the disease now ranks as the most common human papillomavirus-related cancer. Although risk factors have been extensively discussed in the literature, the role of the DNA mismatch repair system remains unanswered. In this context, DNA repair pathways have emerged as an alternative to answer these questions, with the association between dysfunction of the mismatch repair (MMR) DNA repair pathway and the development of cancers being widely reported in several studies addressing different tumors. This study aimed to evaluate the impact of the DNA mismatch repair (MMR) protein immunostaining on the tumor progression and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). This retrospective observational study comprised 50 cases of OPSCC. Immunohistochemistry for MSH2, MSH6, PMS2, MLH1, Ki67, p16 and caspase-3 was performed. The expression of these proteins was assessed in surgical resection margins, primary tumor (PT), and lymph node metastasis (LNM) of p16+ and p16- OPSCC. Clinical-pathological involvement in immunostaining was evaluated with Kruskal-Wallis/Dunn or Mann-Whitney test, Wilcoxon test and Spearman’s correlation. Overall survival (OS) was analyzed with Log-Rank Mantel-Cox and Cox regression. MSH6 and caspase-3 showed high expression in PT (p16+ and p16-) and in LNM (p16+ and p16-), and high levels of MSH2 were found in LNM (p16+ and p16-). An imbalance in MutSα also was observed. PMS2 and caspase-3 expression was associated with poor survival in p16- OPSCC and, in multivariate analysis, MSH2, MSH6 and MLH1 had the poorest prognostic impact in p16+ OPSCC. This retrospective study shed light on the role of MMR proteins in OPSCC cancer progression and prognosis. We evidenced that the overexpression of these proteins is associated with increased DNA mismatch caused by cell proliferation. Thus, MSH2, MSH6 and MLH1 proteins may constitute a protein marker for poor prognosis in patients with p16+ OPSCC.