Preview

Translational Medicine

Advanced search

THE PROLIFERATIVE ACTIVITY (KI-67) AND THE LEVEL OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) GENE EXPRESSION IN GEMISTOCYTIC ASTROCYTOMAS

https://doi.org/10.18705/2311-4495-2018-5-1-44-52

Abstract

Background. Gemistocytic astrocytomas (GA) are a variant of diffuse astrocytomas GII (WHO, 2016), which is characterized by a shorter overall survival of patients than diffuse astrocytoma. The role of vascular endothelial growth factor (VEGF) gene expression and its association with the index of proliferative activity (Ki-67) in GA has not been studied

Objective. To estimate the correlation of VEGF gene expression on Ki-67 in GA.

Design and methods. A retrospective and prospective analysis of morphological and molecular-genetic features of tumors was performed on 9 patients with the diagnosis of GA. Patients over 18 years of age with supratentorial tumor localization were included in the study. The patients were aged from 27 to 37 years, the median age was 32 years. There were 4 men. Fragments of tumor tissue obtained during surgery were subjected to histological, immunohistochemical (Ki-67 and GFAP) and molecular genetic studies. By real-time PCR method was used to determine the level of the VEGF gene expression and the presence of a mutation in IDH1/IDH2 genes. Histological diagnosis was made in accordance with the classification of tumors of the CNS WHO (2016) and the AFIP atlas (2007).

Results. The tumor most often affected several lobes of the brain (44,4%). The first clinical manifestations of the disease in the vast majority of cases were epileptic and hypertensive syndromes (55,6%). For the proliferative activity index Ki-67 >5% (71,4% of cases) the moderate proliferation of vascular endothelium was noted in 85,7% of cases and the middle/high level of VEGF gene expression (except one case). In patients with low Ki-67 (≤5%), the low level of the VEGF gene expression was determined in 100% cases, the proliferation of the vascular endothelium was absent.

Conclusion. High Ki-67 (>5%), the proliferation of the vascular endothelium, middle/high level of VEGF gene expression are typical attributes of anaplastic astrocytomas. That’s why some GA have features of astrocytomas GIII.

About the Authors

A. A. Zrelov
Polenov Russian Scienific Research Institute of Neurosurgery; North-Western State Medical University named after I. I. Mechnikov
Russian Federation

Andrei А. Zrelov - neurosurgeon Polenov RSRIN, the branch of NMRC.

 

Mayakovskaya str. 12, Saint Petersburg,  191014



M. V. Matsko
Polenov Russian Scienific Research Institute of Neurosurgery; Saint-Petersburg Clinical Research Center Specialized Types of Medical Care; Saint Petersburg University; Saint-PetersburgMedico-Social Institute
Russian Federation

Marina V. Matsko - PhD, Senior Researcher, department of Neurooncology Polenov RSRIN, the branch of Almazov NMRC 



D. E. Matsko
Polenov Russian Scienific Research Institute of Neurosurgery; Saint-Petersburg Clinical Research Center Specialized Types of Medical Care; Saint Petersburg University; Saint-PetersburgMedico-Social Institute
Russian Federation
Dmitrii E. Matsko - PhD, prof., Deputy Director, Saint-Petersburg Clinical Research Center Specialized Types of Medical Care


A. Yu. Ulitin
Polenov Russian Scienific Research Institute of Neurosurgery; North-Western State Medical University named after I. I. Mechnikov
Russian Federation

Aleksei Yu. Ulitin - PhD, Director of Polenov RSRIN, the branch of Almazov NMRC



A. O. Baksheeva
Polenov Russian Scienific Research Institute of Neurosurgery; North-Western State Medical University named after I. I. Mechnikov
Russian Federation

Anastasiya O. Baksheeva - postgraduate of NorthWestern State Medical University n. a. I.I. Mechnikov



S. S. Skliar
Polenov Russian Scienific Research Institute of Neurosurgery
Russian Federation

Sof'ya S. Sklyar – postgraduate.

Saint Petersburg



E. N. Imyanitov
North-Western State Medical University named after I. I. Mechnikov; Saint-Petersburg Clinical Research Center Specialized Types of Medical Care; Saint Petersburg University; N.N. Petrov National Medical Research Centre of Oncology
Russian Federation

Evgenii N. Imyanitov - PhD, prof., Head of science department N.N. Petrov RSRIN of Oncology



M. M. Tastanbekov
Polenov Russian Scienific Research Institute of Neurosurgery,
Russian Federation

Malik M. Tastanbekov - PhD, Head of department of Neurooncology Polenov RSRIN, the branch of Almazov NMRC.

Saint Petersburg



References

1. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803-820.

2. Ohta T, Kim YH, Oh JE, et al. Alterations of the RRAS and ERCC1 genes at 19q13 in gemistocytic astrocytomas. J Neuropathol Exp Neurol. 2014;73(10):908-915.

3. Simkin PM, Yang N, Tsui A, et al. Magnetic resonance imaging features of gemistocytic astrocytoma. J Med Imaging Radiat Oncol. 2016;60(6):733-740.

4. Sahm F, Korshunov A, Schrimpf D, et al. Gain of 12p encompassing CCND2 is associated with gemistocytic histology in IDH mutant astrocytomas. Acta Neuropathol. 2017;133(2):325-327.

5. Avninder S, Sharma MC, Deb P, et al. Gemistocytic astrocytomas: histomorphology, proliferative potential and genetic alterations--a study of 32 cases. J Neurooncol. 2006;78(2):123-127.

6. Tihan T, Vohra P, Berger MS, Keles GE. Definition and diagnostic implications of gemistocytic astrocytomas: a pathological perspective. J Neurooncol. 2006;76(2):175-183.

7. Babu R, Bagley JH, Park JG, et al. Low-grade astrocytomas: the prognostic value of fibrillary, gemistocytic, and protoplasmic tumor histology. J Neurosurg. 2013;119(2):434-441.

8. Okamoto Y, Di Patre PL, Burkhard C, et al. Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol. 2004;108(1):49-56.

9. Nowak-Sadzikowska J, Gliński B, Szpytma T, Pluta E. Postoperative irradiation of incompletely excised gemistocytic astrocytomas. Clinical outcome and prognostic factors. Strahlenther Onkol. 2005;181(4):246-250.

10. Martins DC, Malheiros SM, Santiago LH, Stávale JN. Gemistocytes in astrocytomas: are they a significant prognostic factor? J Neurooncol. 2006;80(1):49-55.

11. Kösel S, Scheithauer BW, Graeber MB. Genotypephenotype correlation in gemistocytic astrocytomas. Neurosurgery. 2001;48(1):187-193;

12. Reis RM, Hara A, Kleihues P, Ohgaki H. Genetic evidence of the neoplastic nature of gemistocytes in astrocytomas. Acta Neuropathol. 2001;102(5):422-425.

13. Watanabe K, Peraud A, Gratas C, et al. p53 and PTEN gene mutations in gemistocytic astrocytomas. Acta Neuropathol. 1998;95(6):559-64.

14. Kros JM, Waarsenburg N, Hayes DP, et al. Cytogenetic analysis of gemistocytic cells in gliomas. J Neuropathol Exp Neurol. 2000; 59:679–686.

15. Kros JM, Schouten WC, Janssen PJ, van der Kwast TH. Proliferation of gemistocytic cells and glial fibrillary acidic protein (GFAP)-positive oligodendroglial cells in gliomas: a MIB-1/GFAP double labeling study. Acta Neuropathol. 1996;91(1):99-103.

16. Krouwer HGJ, Davis RL, Silver P, et al. Gemistocytic astrocytomas: a reappraisal. J Neurosurg. 1991;74:399–406.

17. Elvidge AR, Martinez-Coll A. Long-Term FollowUp of 106 Cases of Astrocytoma, 1928–1939. J Neurosurg. 1956;13:230–243.

18. Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005; 64:479–89.

19. Heo YJ, Park JE, Kim HS, et al. Prognostic relevance of gemistocytic grade II astrocytoma: gemistocytic component and MR imaging features compared to non-gemistocytic grade II astrocytoma. Eur Radiol.2017;27(7):3022-3032.

20. Burger PC MD, Scheithauer BW. 7: Tumors of the Central Nervous System. 1 edition. Washington, DC: Amer Registry of Pathology, 2007.

21. Mitiushkina NV, Iyevleva AG, Poltoratskiy AN, et al. Detection of EGFR mutations and EML4-ALK rearrangements in lung adenocarcinomas using archived cytological slides. Cancer Cytopathol. 2013;121(7):370-6.

22. Brandes AA, Nicolardi L, Tosoni A, et al. Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma. Neuro Oncol. 2006;8(3):253-60.


Review

For citations:


Zrelov A.A., Matsko M.V., Matsko D.E., Ulitin A.Yu., Baksheeva A.O., Skliar S.S., Imyanitov E.N., Tastanbekov M.M. THE PROLIFERATIVE ACTIVITY (KI-67) AND THE LEVEL OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) GENE EXPRESSION IN GEMISTOCYTIC ASTROCYTOMAS. Translational Medicine. 2018;5(1):44-52. (In Russ.) https://doi.org/10.18705/2311-4495-2018-5-1-44-52

Views: 3607


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2311-4495 (Print)
ISSN 2410-5155 (Online)