Purpose This systematic review with functional meta-synthesis and exploratory meta-analysis evaluated the clinical utility of molecular testing in ameloblastoma, focusing on diagnostic, genotype–phenotype, prognostic, liquid-biopsy, and precision-therapy implications. Methods PubMed/MEDLINE, Scopus, and Embase were searched from inception to April 2026. Eligible studies were full original articles evaluating direct molecular or molecularly interpretable testing in human ameloblastoma. Data were synthesized using functional meta-synthesis. Exploratory random-effects meta-analyses were performed when sufficient study-level data were available. Results Twenty-nine studies met the inclusion criteria. Molecular testing was most consistently informative for defining the molecular landscape and supporting diagnosis. BRAF V600E was the dominant alteration across the evidence base, but additional alterations in SMO, FGFR2, RAS-family genes, CTNNB1, PIK3CA, EGFR, and ROS1 were reported, particularly in selected or BRAF-wild-type tumors. Exploratory meta-analysis of 19 studies showed a pooled BRAF V600E prevalence of 69.1% (95% CI: 62.1%–75.3%; I2 = 80.3%). Four studies provided complete site-specific data, showing strong enrichment of BRAF V600E in mandibular versus maxillary tumors (OR = 20.13; 95% CI: 7.65–52.95; I2 = 0.0%). BRAF VE1 immunohistochemistry showed high exploratory pooled sensitivity (96.6%; 95% CI: 84.1%–99.4%) and specificity (89.8%; 95% CI: 71.5%–96.8%) when compared with molecular reference methods. Prognostic evidence was inconsistent: BRAF V600E was not a reliable stand-alone recurrence marker, although VEGF mRNA and broader molecular profiles may have prognostic relevance. Plasma cfDNA testing did not reliably detect tissue-positive BRAF V600E. Targeted therapy evidence suggested radiologic response and organ-preservation potential in selected BRAF V600E-mutated tumors, but remained limited to non-randomized series. Conclusions Molecular testing provides clinically relevant diagnostic and genotype–phenotype information in ameloblastoma and may guide targeted therapy in selected cases. Prognostic and liquid-biopsy applications remain insufficiently validated.

Clinical Utility of Molecular Testing in Ameloblastoma: A Systematic Review with Functional Meta-synthesis and Exploratory Meta-analysis

期刊论文
发表日期：

2026年8月5日

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Carlos M. Ardila,
Eliana Pineda-Vélez,
Alejandro I. Díaz-Laclaustra

摘要

Purpose

This systematic review with functional meta-synthesis and exploratory meta-analysis evaluated the clinical utility of molecular testing in ameloblastoma, focusing on diagnostic, genotype–phenotype, prognostic, liquid-biopsy, and precision-therapy implications.

Methods

PubMed/MEDLINE, Scopus, and Embase were searched from inception to April 2026. Eligible studies were full original articles evaluating direct molecular or molecularly interpretable testing in human ameloblastoma. Data were synthesized using functional meta-synthesis. Exploratory random-effects meta-analyses were performed when sufficient study-level data were available.

Results

Twenty-nine studies met the inclusion criteria. Molecular testing was most consistently informative for defining the molecular landscape and supporting diagnosis. BRAF V600E was the dominant alteration across the evidence base, but additional alterations in SMO, FGFR2, RAS-family genes, CTNNB1, PIK3CA, EGFR, and ROS1 were reported, particularly in selected or BRAF-wild-type tumors. Exploratory meta-analysis of 19 studies showed a pooled BRAF V600E prevalence of 69.1% (95% CI: 62.1%–75.3%; I2 = 80.3%). Four studies provided complete site-specific data, showing strong enrichment of BRAF V600E in mandibular versus maxillary tumors (OR = 20.13; 95% CI: 7.65–52.95; I2 = 0.0%). BRAF VE1 immunohistochemistry showed high exploratory pooled sensitivity (96.6%; 95% CI: 84.1%–99.4%) and specificity (89.8%; 95% CI: 71.5%–96.8%) when compared with molecular reference methods. Prognostic evidence was inconsistent: BRAF V600E was not a reliable stand-alone recurrence marker, although VEGF mRNA and broader molecular profiles may have prognostic relevance. Plasma cfDNA testing did not reliably detect tissue-positive BRAF V600E. Targeted therapy evidence suggested radiologic response and organ-preservation potential in selected BRAF V600E-mutated tumors, but remained limited to non-randomized series.

Conclusions

Molecular testing provides clinically relevant diagnostic and genotype–phenotype information in ameloblastoma and may guide targeted therapy in selected cases. Prognostic and liquid-biopsy applications remain insufficiently validated.