Molecular alterations in MAPK/ERK, β-Catenin/Wnt, and PI3K/mTOR pathways in adenomatoid odontogenic tumor
DOI:
https://doi.org/10.1590/1678-7765-2026-0073Keywords:
Adenomatoid odontogenic tumor, KRAS, CTNNB1, PIK3CA, β-catenin, p-mTOR, p-ERK1/2Abstract
Background Previous studies have suggested that tumorigenesis of adenomatoid odontogenic tumor (AOT) may involve the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. However, research on other oncogenic signaling pathways in AOT remains limited.
Objective This study aimed to investigate gene mutations (Kirsten rat sarcoma viral oncogene homolog (KRAS), catenin beta 1 (CTNNB1), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)) and their associated protein expressions (phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2), β-catenin, and phosphorylated mechanistic target of rapamycin (p-mTOR)) in AOT cases. The association between gene mutations and protein expression was also examined.
Methodology In total, eight formalin-fixed, paraffin-embedded AOT tissue samples were manually micro-dissected for DNA extraction. Polymerase chain reaction was performed. Positive samples underwent DNA sequencing. Mutations were analyzed in KRAS exon 2 (codons 12 and 13), CTNNB1 exon 3 (codons 32-45), and PIK3CA exon 9 (codons 542-549). Protein expression was assessed using immunohistochemistry.
Results KRAS mutations (specifically G12R and G12V) were detected in three of the eight cases (37.5%). CTNNB1 mutation (T42I) was identified in one of six cases (16.7%), whereas no PIK3CA mutation was observed. Moreover, moderate expression of p-ERK1/2 and p-mTOR were found in tumor cells of AOT. β-catenin accumulation was detected in seven cases (87.5%), predominantly showing membranous and cytoplasmic localization with no nuclear β-catenin expression. Statistical analysis indicated no association between gene mutations and protein expression.
Conclusions KRAS mutations and p-ERK1/2 expression support a potential role of MAPK/ERK signaling in AOT pathogenesis. The absence of PIK3CA mutations despite p-mTOR expression may in part suggest mutation-independent activation of the PI3K/mTOR pathway. The lack of nuclear β-catenin accumulation may suggest that canonical Wnt signaling is less likely to significantly contribute to AOT tumorigenesis. Further studies with larger cohorts and investigations of additional molecules related to these pathways are warranted.
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