Molecular Markers of Tumor Invasion in Ameloblastoma: A Systematic Review.

BACKGROUND

Ameloblastoma is a benign odontogenic tumor characterized by local aggressiveness and high recurrence rates.

AIM: To identify and classify molecular biomarkers associated with its invasive behavior.

METHODS

Following PRISMA recommendations for Systematic Reviews, a comprehensive search was conducted in PubMed, Scopus, Web of Science, and gray literature for English-language studies published between March 2020 and March 2025. Eligible studies included those using human tissues, retrospective case series, or in vitro assays with experimental validation. Studies focused solely on clinical, radiological, or histopathological aspects were excluded. Risk of bias was assessed using the Joanna Briggs Institute checklist for case series and the QUIN tool for in vitro studies. Data extraction was carried out independently by three reviewers.

RESULTS

A total of 34 studies met the inclusion criteria, identifying 70 biomarkers related to tumor invasion. These were categorized by biological function, with the most commonly reported involved in extracellular matrix degradation, epithelial-mesenchymal transition, bone remodeling, cell proliferation, stemness, and the tumor microenvironment.

CONCLUSIONS

The findings suggest that metalloproteinases, cytokines, and EMT-related proteins are key drivers of invasion. These biomarkers may represent valuable therapeutic targets for developing innovative and less invasive treatment strategies. This review was registered in the Open Science Framework.