Expression of DNMTs and H3K9ac in Ameloblastoma and Ameloblastic Carcinoma

Abstract

Objectives: DNA methyltransferases (DNMTs) and the histone modification H3K9ac are epigenetic markers. This study aimed to describe the immunohistochemical expression of DNMT1, DNMT3A, DNMT3B, and H3K9ac in the dental follicle (DF), ameloblastoma (AME), and ameloblastic carcinoma (AC), correlating these expressions with the recurrence and aggressive behavior in ameloblastoma.Study Design: Immunohistochemical reactions were performed in 10 human DFs, 38 ameloblastomas, and 6 AC samples. Another 59 ameloblastomas assembled in a tissue microarray were used to compare the immunoexpression with the clinical, radiographic, and histopathological characteristics and the presence of BRAFv600e mutation. Each slide was digitized as a high-resolution image and quantified by Aperio ScanScope Nuclear V9 software. All statistical analyzes were performed using GraphPad Prism statistical software.Results: DNMT3B expression was higher in ameloblastomas than in the DFs, while the AC overexpressed all proteins. The ameloblastomas with BRAFv600e mutation, vestibular/lingual, or vestibular/palatine bone cortical disruption and maxilla involvement showed DNMT1 overexpression, while recurrent cases had high DNMT3B levels.Conclusions: DNA methylation and histone modification might play a role in the development, clinical aggressiveness, and recurrence rates of ameloblastoma, such as the progression to AC. Further investigation about gene methylations in ameloblastomas is needed to better understand its relationship with aggressiveness and recurrence.

Case of unicystic ameloblastoma with review of literature

“…PTEN promoter methylation was found in a subset (58.3%) of ameloblastic tumours but did not significantly contribute to decreased PTEN expression. These findings suggest that PTEN inactivation is one of the epigenetic mechanisms underlying the aberrant expression of tumour suppressor genes and contributing to the development of cancer 14–17 …”

“…A valid method for detecting this mutation, either by IHC or molecular assay, usually by PCR, is critical in accurately evaluating mutation occurrence 13 . This study examined the relationship between DNMT and H3K9ac expression and clinical and radiographic features, recurrence, and BRAFv600e mutation in AME 16 …”

“…13 This study examined the relationship between DNMT and H3K9ac expression and clinical and radiographic features, recurrence, and BRAFv600e mutation in AME. 16 It was found that tumours with DNMT1 and DNMT3B overexpression may be more aggressive locally and have a higher risk of recurrence. PTEN promoter methylation was found in a subset (58.3%) of ameloblastic tumours but did not significantly contribute to decreased PTEN expression.…”

“…These findings suggest that PTEN inactivation is one of the epigenetic mechanisms underlying the aberrant expression of tumour suppressor genes and contributing to the development of cancer. [14][15][16][17] Another molecular event in ameloblastoma is the mutation of the BRAF gene, which results in the substitution of amino acid valine (V) by glutamic acid (E) at position 600. This mutation activates MEK/ERK signalling, leading to tumour formation.…”

Immunohistochemical Expression of De novo Methyltransferases (DNMT3A and DNMT3B) in Ameloblastoma and Odontogenic Cysts

“…During the past years, the role of methylation in carcinogenesis and its impact on tumor behavior and progress has been widely explored (Lu et al, 2020). Changes in methylation patterns have been related to the pathogenesis of several tumors including ovarian cancer (Bai et al, 2012), breast cancer (Ben et al, 2012), and oral squamous cell carcinoma (Daniel et al, 2010). However, studies regarding epigenetic events in odontogenic lesions are still scarce.…”