Expression of factors activated by hypoxia, growth factor VEGF, its receptor, carbohydrase IX in tissue in papillary cancers and metastases


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Abstract

Introduction. The molecular mechanisms of the development of tumor pathology of the thyroid gland are associated with the activation of angiogenesis and the development of hypoxia, which contributes to the proliferation, invasion, and progression of the disease. However, the biological characteristics of the development of the disease associated with the involvement of regional lymph nodes are still unknown. The aim of the study. To investigate the transcription factors HIF-1, HIF-2, VHL, growth factors VEGF, CAIX, VEGFR2 expression both in the benign and malignant tumors of the thyroid gland, as well as in the metastatic sites. Material and methods. The study included 40 patients with thyroid pathology who received treatment in the Tomsk National Research Medical Center of the Russian Academy of Science. Stage T1-2N0-2M0 was observed in 18, T3-4N0-2M0 in 22 patients. Regional metastases were diagnosed in 19 patients; the group without regional metastases included 21 patients. The level of gene expression of transcription factors HIF-1, HIF-2, VHL, growth factors VEGF, CAIX, VEGFR2 receptor was evaluated using quantitative reverse transcriptase real-time PCR (RT-qPCR). Results. The work revealed an increase in the level of HIF-1, HIF-2 in the tissue of a malignant thyroid tumor compared with patients with benign tumors. The expression of molecular markers in the tissue of papillary thyroid cancer was not associated with clinical and morphological indices of the disease. In the tissue of thyroid metastases, a decrease in the level of VHL B VEGF mRNA was noted in comparison with the primary tumor. In patients with papillary thyroid cancer with an increased level of VHL mRNA (>1), the expression of HIF-1, HIF-2, and VEGF, CAIX is higher compared with patients with a reduced level of VHL (<1). Moreover, the distribution frequency, depending on the level of expression of the VHL protein, does not practically differ in groups of patients with a tumor of various sizes and the spread of the disease to regional lymph nodes. Conclusion. There was reveled significance of molecular markers associated with angiogenesis: transcription factors HIF-1, HIF-2, VEGF, VEGFR2 and CAIX in the development of benign and malignant thyroid tumors, as well as in the spread of the disease. The formation of metastases in regional lymph nodes is determined by a change in the expression of the VHL protein, which is accompanied by an increase in the expression of angiogenic factors.

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About the authors

L. V Spirina

Tomsk National Research Medical Center; Siberian State Medical University

Email: spirinalvl@mail.ru
Leader Researcher, Professor. Tomsk National Research Medical Center of the Russian Academy of Sciences, Cancer Research Institute; Siberian State Medical University. Docent. Doctor of Medical Sciences Kooperativnaya str., 5, Tomsk, 634050, Russian Federation; Moskovsky trakt, 2, Tomsk, 634050, Russian Federation

K. S Malysheva

Siberian State Medical University

Email: taraz-kr@mail.ru
Student Moskovsky trakt, 2, Tomsk, 634050, Russian Federation

S. U Chizhevskaya

Tomsk National Research Medical Center; Siberian State Medical University

Email: sch@oncology.tomsk.ru
leading researcher; associate Professor of the Department of Oncology. Tomsk National Research Medical Center of the Russian Academy of Sciences, Cancer Research Institute; Siberian State Medical University. Doctor of medicine Kooperativnaya str., 5, Tomsk, 634050, Russian Federation; Moskovsky trakt, 2, Tomsk, 634050, Russian Federation

I. V Kondakova

Tomsk National Research Medical Center

Email: kondakova@oncology.tomsk.ru
Head of Laboratory of Tumor Biochemistry. Tomsk National Research Medical Center of the Russian Academy of Sciences, Cancer Research Institute. Professor, Doctor of Medical Sciences Kooperativnaya str., 5, Tomsk, 634050, Russian Federation

I. V Kovaleva

Siberian State Medical University

Email: irina.kovalyova.kovaleva@mail.ru
Student Moskovsky trakt, 2, Tomsk, 634050, Russian Federation

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