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

• Gleyson Kleber do Amaral-Silva ^[2] ; Laryssa Moura Dias ^[2] ; Bruno Augusto Linhares Almeida Mariz ^[2] ; Felipe Paiva Fonseca ^[1] ; Ana Lúcia Carrinho Ayroza Rangel ^[3] ; Virgílio Gonzales Zanella ^[4] ; Rogerio Moraes Castilho ^[5] ; Manoela Domingues Martins ^[6] ; Pablo Agustin Vargas ^[7] ; Vivian Petersen Wagner ^[8]
  1. [1] Universidade Federal de Minas Gerais

     Universidade Federal de Minas Gerais

     Brasil

     
  2. [2] Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil
  3. [3] Department of Pathology, State University of Western Paraná, Cascavel, PR, Brazil
  4. [4] Head and Neck Surgery Department, Santa Rita Hospital, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil
  5. [5] Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil; Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA
  6. [6] Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil; Department of Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
  7. [7] Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil; Department of Oral Pathology and Oral Biology, School of Dentistry, University of Pretoria, Pretoria, South Africa
  8. [8] Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil; Academic Unit of Oral and Maxillofacial Medicine and Pathology, Department of Clinical Dentistry, University of Sheffield, Sheffield, UK

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• Localización: Medicina oral, patología oral y cirugía bucal. Ed. inglesa, ISSN-e 1698-6946, Vol. 27, Nº. 2 (March), 2022
• Idioma: inglés
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• Resumen

  • 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 MutSα (hMSH2-hMSH6) and MutSβ (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.

    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 MutSαhigh and MutSβhigh based on hMSH2-hMSH6 and hMSH3-hMSH6 expression, respectively.

    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 MutSαhigh expression had lower disease-free survival compared to MutSαlow cases. A 10.26-fold increased risk of presenting local recurrence was observed.

    Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutSα overexpression predicts a poor clinical outcome in malignant SGT.