Estudo molecular do carcinoma epitelial-mioepitelial da glândula salivar

Abstract

Epithelial-myoepithelial carcinoma (EMC) is an uncommon, low-grade malignant neoplasm, predominantly affecting the parotid gland. It has slow growth and low metastatic potential. Although uncommon, transformation to high-grade patterns can occur, negatively impacting prognosis. Mutations in the HRAS, PIK3CA, and AKT genes have been described in EMC. These mutations may be associated with activation of the Ras pathway and the downstream RAF/MEK/ERK (MAPK) and PI3K/AKT/mTOR (PI3K) pathways, responsible for processes such as cell proliferation, survival, and tumor progression. However, the impact of mutations in EMC on the expression of Ras pathway genes and its canonical and non-canonical downstream pathways, and the Ras pathway role in the pathobiology of EMC, remains unknown. This study aimed to investigate the gene expression of Ras pathway components in EMC samples by RT-qPCR, in addition to performing functional enrichment analyses and characterizing the samples for mutations in the PIK3CA gene. Gene expression analysis in EMC (n = 8) revealed overexpression of the genes FOS and JUN, while PLD1, MAPK9, MAP2K3, RALB, MAPK6, PIK3CB and VEGFC showed reduced expression compared to the control (normal salivary gland, n = 4). Functional analysis indicated greater enrichment mainly of the MAPK signaling pathway. The mutation in exon 20 (p.H1047R) of the PIK3CA gene was analyzed in 5 of the 8 samples included in RT-qPCR analysis and in 5 additional samples, and no mutation was found. These findings reinforce the role of the Ras pathway, especially the downstream MAPK pathway, and the AP-1 transcription factor (composed of JUN and FOS) in the molecular context of EMC. These results may inform the development of future diagnostic and therapeutic strategies.