Influence of molecular genetic factors on the prognosis of localized and locally advanced adrenocortical cancer in children

Materials and methods. The study included 18 samples of patients with ACC stages I–III who received treatment from 2003 to 2021. Samples from 6 (33 %) patients with stage I, 5 (28 %) patients with stage II, and 7 (39 %) patients with stage III ACC were analyzed. The average age of patients is 61.6 (12–216) months. Four subgroups of patients were identified: with an isolated mutation in the TP-53 gene, with an isolated mutation in the IGF-2 gene, with simultaneous mutations in the TP-53 and IGF-2 genes and no mutations in the studied genes.
Results. In 12 out of 18 (67 %) of the studied samples, mutations in the TP-53 and IGF-2 genes and their combination were detected. A mutation in the TP-53 gene was present in 8 patients, in the IGF-2 gene in 8 patients, and a combination of TP-53 + IGF-2 in 4 patients. The five-year OS and DFS in the groups of patients with mutations in TP-53 and/or IGF-2 were 45.5 % and 41.6 % versus 83.3 % and 83.3 % in the group without mutations (p = 0.15 and p = 0.18, respectively). The five-year overall (OS) and disease-free (DFS) survival in the TP-53 group compared with the group without the mutation was 50 % and 50 % versus 62.2 % and 66.7 % (p = 0.6 and p = 0.5, respectively). The five-year OS and DFS in the IGF-2 group compared with the group without mutation was 14.3 % and 0 % versus 90 % and 90 % (p = 0.001 and p = 0.0009, respectively). The five-year OS and DFS in the group in which the combination of mutations in the TP-53 + IGF-2 genes was present compared with patients without the combination of these mutations was 0 % vs. 75.2 % and 76.9 % (p = 0.002 and p = 0.003, respectively).
Conclusion. The presence of a mutated IGF-2 gene is combined with a high Ki-67 index and is a factor in poor prognosis in children with localized forms of ACC. The simultaneous presence of mutations in the TP-53 and IGF-2 genes in the tumor also significantly negatively affects survival rates. Further prospective studies are needed to confirm the data and develop tactics for this group of patients.

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