Is there a role for impaired DNA mismatch repair system in the pathogenesis of ameloblastomas? A scoping review

Deficiencies in the DNA mismatch repair (MMR) system are associated with several human neoplasms. However, the role of MMR alterations in ameloblastoma pathogenesis remains poorly understood. This scoping review aimed to synthesize the available evidence on the expression patterns of MMR proteins in ameloblastomas and to discuss their potential biological and clinical implications.

This scoping review was conducted in accordance with the PRISMA-ScR guidelines and registered in PROSPERO (CRD420251150967). A comprehensive literature search was performed in PubMed/MEDLINE, Web of Science, Embase, and Scopus to address the following question: "What is the expression pattern of DNA mismatch repair system proteins in ameloblastomas?". Cross-sectional studies, cohort studies, case-control studies, and case series were included, without restrictions on publication date or language. Qualitative and quantitative data were systematically extracted, tabulated, and synthesized.

The search retrieved 97 articles. Five studies met the eligibility criteria, comprising a total of 271 ameloblastoma samples. A relatively consistent pattern of MMR protein expression was observed across studies. Ameloblastomas showed reduced expression of MMR proteins compared with tooth germ controls, with more pronounced alterations in conventional than in unicystic ameloblastomas. Changes in MMR expression were potentially associated with tumor proliferative activity, risk of recurrence, and the presence of BRAF mutations.

Altered expression of MMR proteins appears to be involved in key aspects of ameloblastoma biology, including genomic stability, tumor proliferation, and recurrence risk. Further studies are needed to clarify the potential role of MMR dysregulation as a clinically relevant biomarker in ameloblastomas.