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

Author(s)

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

• Document type: Journal article
• Source: MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL; v. 27, n. 2, p. 10-pg., 2022-03-01.

Abstract

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)

• FAPESP's process: 09/53839-2 - Creation of a Digital Pathology Laboratory using a histological slidescanner
• Grantee: Oslei Paes de Almeida
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 17/08995-2 - Epigenetic events in ameloblastomas: immuno-expression of DNMT1, DNMT3b and H3K9ac and hMutS promoters' methylation profile
• Grantee: Gleyson Kleber do Amaral Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/12435-5 - HMutSB immunoexpression in salivary gland tumors
• Grantee: Laryssa Moura Dias
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/21520-8 - Analysis of the expression of proteins related to DNA repair, anti-apoptosis and cellular proliferation in ameloblastoma and ameloblastic carcinoma
• Grantee: Gleyson Kleber do Amaral Silva
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/21785-4 - Association of BDNF/TRKB signaling pathway with tumor agressiveness and cancer stem cell profile of malignant salivary gland tumors
• Grantee: Vivian Petersen Wagner
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/24715-2 - FGF-2, FGFR-1, PI3K, Akt and COX-2 expression in Oral Leucoplakia, primary and metastatic Oral Squamous Cell Carcinoma
• Grantee: Bruno Augusto Linhares Almeida Mariz
• Support Opportunities: Scholarships in Brazil - Doctorate