IMMUNOHISTOCHEMICAL STUDY OF TRANSCRIPTION FACTORS NEUROD1, PROX1, FOXM1, SOMATOSTATIN, AND CXCR4 RECEPTORS, CD38 IN GLIOBLASTOMAS TO DEVELOP NEW APPROACHES FOR THE TARGETED THERAPY


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Currently, glioblastoma is an extremely malignant tumor, for which treatment only temozolomide is relatively effective. Aim to study the expression and variants of coexpression of transcription factors NeuroD1, Prox1, FoxM1, somatostatin receptors of the 2nd and 5th type, CD38 and CXCR4 receptors in glioblastoma. The methods included an immunohistochemicalstudy with antibodies to Neuro1l, CXCR4, Prox1, FoxM1, CD38, SSTR2, SSTR5and morphometric analysis of glioblastoma fragments from 22 patients (surgical material). Results. A high level of expression (>50% of the cells) of FoxM1 was detected in 85,7% of glioblastomas samples. The average expression level of FoxM1 accouned of 82,8±5,5%. NeuroD1 was expressed in the nuclei of glioblastoma cells in l00% of cases, the average level of its expression was 95,4±0,7%. High levels of CXCR4 expression were detected in l6 tumors (76,2%). The average expression level of CXCR4 was 76,2±6,1%. Proxl was expressed in 57,l% of cases with an average expression level of 58,4±7,0%. All of the above proteins were found in the tumor cells and the walls of its vessels. SSTRs of the 2nd and 5th types were expressed in the cells of the vascular walls in all cases, the expression level was 2,2±1,1 and 6,7±1,2%, respectively. Marked expression of CD38 was observed in only 9,5% of cases. The average level of expression of CD38 - l0,8±3,4%. When analyzing combinations of marker expression, FoxM1+/NeuroD1+/Prox1-/CXCR4+/ CD38- immunophenotype was most often found (in 38,1% of cases). Conclusion. As a result of the study, the expression of CD38 was detected for the first time in glioblastoma cells. High levels of expression of the studied proteins were recorded in the tumor cells and in walls of its vessels. The immunophenotypic heterogeneity of glioblastoma was determined, the most common variant of protein combination in one tumor, FoxM1+/NeuroD1+/Prox1-/CXCR4+/CD38-, was revealed. According to the data obtained, a new personalized approach to treatment is required with the definition of targets for exposure and the corresponding spectrum of drugs in each individual case.

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作者简介

B. Galkovsky

Almazov National Medical Research Centre

Email: lubamitr@yandex.ru
Russian Federation, St. Petersburg

L. Mitrofanova

Almazov National Medical Research Centre

Email: lubamitr@yandex.ru
Russian Federation, St. Petersburg

D. Gulyaev

Almazov National Medical Research Centre

Email: lubamitr@yandex.ru
Russian Federation, St. Petersburg

Y. Lakhina

Almazov National Medical Research Centre

Email: lubamitr@yandex.ru
Russian Federation, St. Petersburg

Y. Osipov

Almazov National Medical Research Centre

Email: lubamitr@yandex.ru
Russian Federation, St. Petersburg

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