MutS alpha expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study

Autor(es)

do Amaral-Silva, Gleyson Kleber ; Dias, Laryssa Moura ; Linhares Almeida Mariz, Bruno Augusto ; Fonseca, Felipe Paiva ; Carrinho Ayroza Rangel, Ana Lucia ; Zanella, Virgilio Gonzales ; Castilho, Rogerio Moraes ; Martins, Manoela Domingues ; Vargas, Pablo Agustin ; Wagner, Vivian Petersen

• Tipo de documento: Artigo Científico
• Fonte: MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL; v. 27, n. 2, p. 10-pg., 2022-03-01.

Resumo

Background: Appropriate DNA replication is vital to maintain cell integrity at the genomic level. Malfunction on DNA repair mechanisms can have implications related to tumor behavior. Our aim was to evaluate the expression of key complexes of the DNA mismatch-repair system MutS alpha (hMSH2-hMSH6) and MutS beta (hMSH2-hMSH3) in a panel comprising the most common benign and malignant salivary gland tumors (SGT), and to determine their association with disease-free survival. Material and Methods: Ten cases of normal salivary gland (NSG) and 92 of SGT (54 benign and 38 malignant) were retrieved. Immunohistochemistry was performed for hMSH2, hMSH3, hMSH6. Scanned slides were digitally analyzed based on the percentage of positive cells with nuclear staining. Cases were further classified in MutS alpha(high) and MutS beta(high) based on hMSH2-hMSH6 and hMSH3-hMSH6 expression, respectively. Results: hMSH3 expression was lower in malignant SGT compared to NSG and benign cases. Adenoid cystic carcinoma (ACC) cases with perineural invasion presented a lower percentage of hMSH3 positive cells. hMSH6 was downregulated in both benign and malignant SGT compared to NSG. Malignant SGT cases with MutS alpha(high) expression had lower disease-free survival compared to MutS alpha(high )cases. A 10.26-fold increased risk of presenting local recurrence was observed. Conclusions: Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutS alpha overexpression predicts a poor clinical outcome in malignant SGT. (AU)

• Processo FAPESP: 09/53839-2 - Criação do Laboratório de Patologia Digital através do uso do escaneador de lâminas histológicas (Aperio® Scanscope CS)
• Beneficiário: Oslei Paes de Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 17/08995-2 - Eventos epigenéticos em ameloblastomas: imunoexpressão de DNMT1, DNMT3b e H3K9ac e perfil de metilação de promotores hMutS
• Beneficiário: Gleyson Kleber do Amaral Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/12435-5 - Imunoexpressão de hMutSB em tumores de glândulas salivares
• Beneficiário: Laryssa Moura Dias
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/21520-8 - Análise da expressão de proteínas relacionadas ao reparo do DNA, anti-apoptose e proliferação celular em ameloblastoma e carcinoma ameloblástico
• Beneficiário: Gleyson Kleber do Amaral Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 16/21785-4 - Relação da via de sinalização BDNF/TRKB com a agressividade e perfil de células tronco tumorais de neoplasias malignas de glândula salivar
• Beneficiário: Vivian Petersen Wagner
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/24715-2 - Expressão de FGF-2, FGFR-1, PI3K, Akt e COX-2 em Leucoplasia Oral e Carcinoma Espinocelular Oral primário e metastático
• Beneficiário: Bruno Augusto Linhares Almeida Mariz
• Modalidade de apoio: Bolsas no Brasil - Doutorado