THE OBJECTIVE
Of study was expression profiles of 17 candidate genes in cells of morphologically verified myomatous nodes and unchanged myometrium in the associated and non-associated molecular phenotype of uterine fibroids with mutations in the MED12 gene.
MATERIAL AND METHODS
The research material was presented by 133 tissue samples obtained as a result of surgical treatment, of which 85 samples of myomatous nodes and 48 samples of morphologically unchanged myometrium. All samples of myomptous nodes were analyzed for the presence of somatic mutation MED12 by Sanger sequencing. Using reverse transcription and polymerase chain reaction (PCR) methods. The expression profile of 17 candidate genes (PAPPA1, GRPR, TYMS, PLAG1, VCAN, AVPR1A, ESR1, PLA2R1, RANKL, KLF11, KRT19, MMP11, ADAM12, MMP16, PCP4, SATB2, WIF1), presumably involved in the pathogenesis of uterine fibroids, selected based on bioinformatic analysis, was studied. For histological examination, sections with a thickness of 5 microns were obtained from paraffin blocks and stained with hematoxylin and eosin. An immunohistochemical study was performed to determine the surrogate molecular subtype of leiomyoma samples.
RESULTS AND DISCUSSION
This report presents data indicating that for different molecular phenotypes of uterine fibroids associated and not associated with somatic mutations in the MED12 gene (MED12+ and MED12–, respectively), the expression profile of certain genes is significantly different. Hyperexpression of the HMGA2 gene is observed in some myomatous nodes with the molecular phenotype MED12–, and in some — decreased expression of the HMGA2 gene. The expression profile of other candidate genes in myomatous nodes of MED12– with increased/decreased expression of the HMGA2 gene also differs. In addition, according to immunohistochemical studies, hypervascularization and increased cellularity are detected in 39% of samples of myomatous nodes with the molecular phenotype MED12– and HMGA2+ more often than in samples of myomatous nodes with the molecular phenotype MED12– and HMGA2.
