Expression of hMLH1 and hMSH2 proteins in ameloblastomas and tooth germs

Abstract

BackgroundMismatch repair proteins (MMRPs) are a group of nuclear enzymes that participate in the repair of base mismatches that occur during DNA replication in all proliferating cells. The most studied MMRPs are hMSH2 and hMLH1, which are known to be highly expressed in normal tissues. A loss of MMRPs leads to the accumulation of DNA replication errors in proliferating cells. Ki-67 is a biomarker regarded to be the gold-standard tool for determining cell proliferation by immunohistochemical methods. The aim of this study was to investigate the immunohistochemical expression of hMLH1, hMSH2 and Ki-67 proteins in ameloblastomas and tooth germs, to contribute to the understanding of the development of this odontogenic neoplasm.Material and MethodsImmunohistochemical assays to determine the presence of proteins hMSH2, hMLH1 and Ki-67 were performed in 80 ameloblastomas (40 solid and 40 unicystic) and five tooth germs.ResultsUnicystic ameloblastomas showed higher MMRP expression (hMLH1: 62.5 ± 43.4; hMSH2: 83.3 ± 47.8) than did solid ameloblastomas (hMLH1: 59.4 ± 13.5; hMSH2: 75.8 ± 40.2). Additionally, the cell proliferation index assessed by Ki-67 was inversely proportional to the expression of MMRP. Comparison between tooth germs and ameloblastoma revealed significantly higher expression of hMLH1, hMSH2 and Ki-67 in tooth germs (p=0.02).ConclusionsThe differences of MMRP and Ki-67 immunoexpression between ameloblastomas and tooth germ suggest that alterations in the MMRP mechanisms could participate in the biological behavior of ameloblastomas. Key words:hMLH1, hMSH2, Ki-67, Ameloblastomas, Tooth germs.

DNA methylation status of MutS genes in ameloblastoma

“…Interestingly, dental follicles showed a similar profile. According to these data, the lower MSH2/MSH6 immunohistochemical expression reported in ameloblastoma (Amaral‐Silva et al., 2017; Bologna‐Molina et al., 2018) could not be explained exclusively by the regulation of the gene promoters' methylation. MSH2 and MSH6 showed a negative correlation between the methylation status and their respective immunohistochemistry expression, similar to that observed in sporadic colorectal cancer (Malhotra et al., 2014).…”

“…The MMR alterations were reported in several human diseases, mainly associated with Lynch Syndrome (Cerretelli et al., 2020). The ameloblastoma showed low expression of MSH2, MSH6 and MLH1 compared to the normal odontogenic tissue (Amaral‐Silva et al., 2017; Bologna‐Molina et al., 2018). MSH2 and MLH1 gene mutations were not observed in this tumour, which suggests that other molecular events, such as epigenetic alterations, could play a role in the regulation of the proteins (Bologna‐Molina et al., 2018).…”

“…At the same time, the MSH2, MSH3 and MSH6 overexpressions are present in cases with recurrence and the BRAF‐V600E mutation (Amaral‐Silva et al., 2017). Because Bologna‐Molina et al did not find MSH2 mutations that justify the low expression in the ameloblastoma cell lines, they hypothesised that abnormal epigenetic mechanisms might regulate this MutS protein in the tumour (Bologna‐Molina et al., 2018).…”

Bases moleculares de los tumores odontogénicos benignos: revisión de la literatura en el contexto de la última clasificación de la Organización Mundial de la Salud

“…A partir de este último estudio se puede inferir una relación entre los cambios en las proteínas responsables de identificar y corregir el daño del ADN con el desarrollo de ameloblastomas, lo que refuerza la necesidad de más estudios sobre el tema y demuestra que existen controversias en la defini-ción de los aspectos moleculares de los TOs. En este contexto, en otro importante estudio desarrollado por Bologna-Molina et al (43) se evaluaron las expresiones inmunohistoquímicas de las proteínas reparadoras del ADN hMLH1 y hMSH2 y del Ki-67 en ameloblastomas y gérmenes dentarios. El estudio incluyó 40 ameloblastomas convencionales, 40 ameloblastomas uniquísticos y cinco gérmenes dentarios.…”