Neuroblastoma and ganglioneuroblastoma of the central nervous system in adult patients: clinical and molecular genetic aspects
https://doi.org/10.56618/2071-2693_2023_15_3_77
Abstract
SUMMARY. Neuroblastoma (NB) and ganglioneuroblastoma (GNB) of the central nervous system are rare (1 % of all tumors) and poorly studied malignant embryonic tumors in adult patients. Now, the molecular genetic features of tumors and the prognosis of the disease for adult patients have not been sufficiently studied, and there are no generally accepted standards of therapy.
PURPOSE OF THE STUDY. To identify factors that affect progression-free survival (PFS) and overall survival (OS) of adult patients with NB and GNB based on the study of their clinical and morphological characteristics, treatment parameters, and molecular genetic profile.
MATERIALS AND METHODS. A retro-prospective study was conducted, which included 15 patients with NB and 16 patients with GNB aged 18 years and older. The histological diagnosis was established after immunohistochemical examination of the tumor material (staining for Syn, NSE, GFAP, CD 99, Ki67). Real-Time PCR was used to evaluate mRNA expression of TP, MGMT, ERCC 1, PDGFR-α, VEGF, C-kit, and β-tubulin III genes. Patients were studied clinical and molecular genetic characteristics, treatment approaches and long-term results.
RESULTS. Patients with GNB had both a higher risk of recurrence (HR = 2.67; 95 % CI 1.10–6.47; p = 0.022) and a higher risk of death (HR = 8.88; 95 % CI 1.99–39.50; p = 0.00045), compared with patients with NB. Given the difference in survival between NB and GNB, further statistical analysis was performed separately for each group of patients. Thus, in patients with NB, tumor removal of 50 % or more increased OS compared to biopsy by 37.0 months (p = 0.042). While in patients with GNB, total tumor resection increased both PFS by 10.8 months and OS by 28.3 months, even compared with subtotal resection (p = 0.014 and p = 0.017, respectively). In the group of patients with GNB, chemotherapy (ChT) in the amount of 6 cycles with temozolomide increased the FFS and OS compared with other chemotherapy regimens (p=0.026 and p=0.025, respectively). According to the results of molecular genetic profiling of tumors, the absence of a high level of expression of the VEGF gene in NB attracted attention. In GNB, a high level of expression was found in the PDGFR-α (53.8 %, 7/13), VEGF (53.8 %, 7/13) and β-tubulin III (84.6 %, 11/13) genes. Expression of VEGF above the average level (ΔCt < –1.0) significantly increased the risk of recurrence and death both in the general group of patients and in the GNB group.
CONCLUSION. The morphological type of the tumor significantly influenced the duration of PFS and OS in adult patients. The radical nature of surgical treatment affected survival in both groups, but especially in the group of patients with GNB. In patients with GNB, chemotherapy in the amount of 6 cycles with temozolomide increased the PFS and OS. The key molecular genetic prognostic marker in adult patients with GNB is the VEGF gene.
About the Authors
A. S. NechaevaRussian Federation
Anastasia Sergeevna Nechaeva
Mayakovskogo st., 12, St. Petersburg, 191014
Akkuratova st., 2, St. Petersburg, 197341
M. V. Matsko
Russian Federation
Marina Vitalievna Matsko
Leningradskaya st., 68a lit. A, St. P etersburg, 197758
7–9, St Petersburg, 199034
Kondratievsky pr., 72, lit. A, St. P etersburg, 195271
A. Yu. Ulitin
Russian Federation
Alexey Yurievich Ulitin
Mayakovskogo st., 12, St. Petersburg, 191014
Kirochnaya st., 41, St. Petersburg, 191015
E. N. Imyanitov
Russian Federation
Evgeny Naumovich Imyanitov
Leningradskaya st., 68, St. Petersburg, 197758
Litovskaya st., 2, St. Petersburg, 194100
A. G. Iyevleva
Russian Federation
Aglaya Gennadievna Iyevleva
Leningradskaya st., 68, St. Petersburg, 197758
I. V. Bizin
Russian Federation
Ilya Valeryevich Bizin
Leningradskaya st., 68, St. Petersburg, 197758
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Review
For citations:
Nechaeva A.S., Matsko M.V., Ulitin A.Yu., Imyanitov E.N., Iyevleva A.G., Bizin I.V. Neuroblastoma and ganglioneuroblastoma of the central nervous system in adult patients: clinical and molecular genetic aspects. Russian Neurosurgical Journal named after Professor A. L. Polenov. 2023;15(3):77-87. (In Russ.) https://doi.org/10.56618/2071-2693_2023_15_3_77