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. 2022 Mar 1;27(2):e164-e173.
doi: 10.4317/medoral.25138.

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

G-K Amaral-Silva  1 , L-M Dias, B-A Mariz, F-P Fonseca, A-L Rangel, V-G Zanella, R-M Castilho, M-D Martins, P-A Vargas, V-P Wagner
Affiliations

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

G-K Amaral-Silva et al. Med Oral Patol Oral Cir Bucal. .

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 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.

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 MutSαhigh and MutSβhigh 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 MutSαhigh expression had lower disease-free survival compared to MutSαlow 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 MutSα overexpression predicts a poor clinical outcome in malignant SGT.

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Conflict of interest statement

Conflicts of interest The authors declare that have no conflict of interest. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the paper.

Figures

Figure 1
Figure 1
Representative images of hMSH2, hMSH3, and hMSH6 immunoexpression in Normal Salivary Glands, Pleomorphic Adenoma, Warthin Tumor, Adenoid Cystic Carcinoma, and Mucoepidermoid Carcinoma.
Figure 2
Figure 2
(A) Scatter plot of MutSβ complex (hMSH2 and hMSH3). (B) Scatter plot of MutSα complex (hMSH2 and hMSH6). Spearman's correlation coefficient and p values are detailed for each correlation considering all diagnoses combined.
Figure 3
Figure 3
Kaplan-Meier cumulative survival curves for disease-free survival according to (A) Clinical Stage, (B) Perineural Invasion, (C) MutSα expression and (D) MutSβ expression (p values of the log-rank test).
See this image and copyright information in PMC

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