[Pituitary adenomas: a pathway to understanding the aggressive form. Clinical genetic analysis of potential prognostic markers in the development of aggressive pituitary adenomas].

Abstract

Background: Currently, due to the lack of clear criteria for predicting the aggressive course of pituitary adenomas (APA), the search for diagnostic markers is highly relevant. Genetic markers, among others, may serve as such markers since their identification is possible at early stages of the pathological process.

Objective: To study the prevalence of genotypic polymorphisms G634C of the VEGFA gene (locus rs2010963), C/T of the TP53_2 gene (locus rs17884159), C/T of the HIF1A gene (locus rs11549465), and G-197A of the IL-17A gene in a sample of patients with APA and their association with the development of various clinical variants of the aggressive course of the disease.

Materials and methods: The study included 100 patients with a clinically confirmed diagnosis of pituitary adenoma (main group) and 83 practically healthy individuals (control group). The polymorphism of the studied genes was analyzed using allele-specific polymerase chain reaction (PCR) with SNP-Express reagent kits in real-time mode ("Sintol", Russia). The interpretation of the results was carried out using the "RotorGene" software of the PCR-RV device. The study also included general clinical, biochemical, and hormonal tests, as well as instrumental and neuroimaging methods, including magnetic resonance imaging (MRI) of the chiasmatic-sellar region and statistical analysis.

Results: The study showed that the heterozygous mutation (G/C) of the G634C VEGFA polymorphism was recorded in 21 cases (26%), and the homozygous mutation with a complete replacement of guanine (G) by cysteine (C) at position 634 (C/C) was detected in 4 cases. In patients with invasive pituitary adenomas (PA), the heterozygous variant (G/C) was twice as frequent - 32.7% (n=17) compared to the control group - 15.7% (n=13). The homozygous genotype (C/C) was also more frequently observed in patients with invasive PA growth - 7.7% (n=4) compared to the control group.The heterozygous variant (C/T) of the HIF1A gene was significantly more common (p=0.02) in patients with invasive adenomas compared to the control group: 25% (n=13) and 9.8% (n=8), respectively. In non-invasive PAs, this genotype was observed three times less frequently. The study of TP53_2 polymorphism (locus rs17884159) showed that in patients with invasive PAs, the frequency of the heterozygous variant (C/T) was significantly higher - 15.4% (n=8) compared to the control group - 4.8% (n=4).

Conclusion: The conducted genetic analysis of polymorphisms in the VEGFA, HIF1A, TP53_2, and IL-17A genes revealed significant deviations, confirming their practical significance in the early diagnosis of aggressive pituitary adenomas.