CLINICAL ANALYSIS OF SERUM INTERLEUKIN-16 AND VASCULAR ENDOTHELIAL GROWTH FACTOR LEVELS DEPENDING ON MORPHOLOGICAL CHARACTERISTICS OF THE TUMORS AND LONG-TERM TREATMENT OUTCOMES IN PATIENTS WITH BONE NEOPLASMS

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Abstract

Background: The progress in cancer treatment, including bone malignancies, is associated with advances in molecular biology. Based on the results of a  number of studies, treatment of bone sarcomas have been expanded with targeted therapy that uses drugs with targeted actions, including anti-angiogenic and bevacizumab, in particular. It inhibits the binding of a key activator of neoangiogenesis, vascular endothelial growth factor (VEGF), with its receptors type 1 and 2 (Flt-1 and KDR) on the surface of endothelial cells, which results in a  decrease in vascularization and in inhibition of tumor growth. Beyond VEGF, other activators of neoangiogenesis have been identified, such as interleukin 16 (IL-16). Aim: To compare baseline serum IL-16 and VEGF in patients with malignant, borderline and benign bone tumors. Materials and methods: Serum IL-16 and VEGF levels was compared in 138 patients with primary bone tumors: benign (n=10); borderline (giant cell bone, n=22); malignant (n=106), aged 14 to 50 years, by immunoenzyme assay (Biosource, USA for IL-16 and R&D, USA for VEGF) before any specific treatment. Bone malignancies were identified as osteosarcoma (n=45, among them 35  typical, 6 parosteal, and 4 periosteal), chondrosarcoma (n=24), Ewing sarcoma (n=27), and undifferentiated pleomorphic sarcoma (n=7) and chordoma (n=3). Results: The rate of IL-16 identification in the serum of bone tumors patients was 93%, with no significant differences depending on the histological structure of the tumor. No association between the size of primary tumors and IL-16 serum levels was found. Overall 3 and 5-year survival of patients with malignant bone tumors with IL-16 serum levels>33 pg/mL was significantly lower than in those IL-16 levels of≤33 pg/mL. Overall 5-year survival in osteosarcoma patients with higher IL-16 serum levels 1.6-fold lower, in Ewing sarcoma patients, 1.7-fold lower, and in chondrosarcoma patients, 1.8-fold lower than that the patients with IL-16 levels of≤33 pg/mL. VEGF levels in bone sarcomas patients were significantly higher than in those with borderline and benign tumors, whereas statistical analysis did not find any significant difference in VEGF levels depending on the histological structure of the primary tumor. Maximal VEGF levels were found in periosteal osteosarcoma, minimal ones, in parosteal osteosarcoma. Overall 3 and 5-year survival of patients with bone malignancies and serum VEGF concentrations above the mean for the group (> 493 pg/mL) was higher than that in the patients with low VEGF levels. Similar results were obtained in osteosarcoma, whereas in Ewing sarcoma and chondrosarcoma higher 3 and 5-year survival rates were observed in patients with serum VEGF levels below 493 pg/mL. Conclusion: These data suggest that IL-16 and VEGF expression could be associated with pathophysiological changes related to growth and metastatic process of bone sarcomas, and may be a subject for further studies to determine the levels of these biomarkers and their predictive value in bone malignancies.

About the authors

I. V. Babkina

N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Author for correspondence.
Email: docbabkina@rambler.ru
MD, PhD, Professor, Leading Research Fellow, Clinical Biochemistry Laboratory Russian Federation

A. A. Alferov

Moscow State University of Medicine and Dentistry named after A.I. Evdokimov; 20–1 Delegatskaya ul., Moscow, 127473, Russian Federation

Email: docbabkina@rambler.ru
MD, Postgraduate Student, Chair of Clinical Biochemistry and Laboratory Diagnostics, Faculty of Additional Professional Education Russian Federation

A. V. Bondarev

Moscow City Cancer Hospital No 62; 27 poselok Istra, p/o Stepanovskoe, Krasnogorskiy rayon, Moskovskaya oblast', 143423, Russian Federation

Email: docbabkina@rambler.ru
MD, Orthopaedic Surgeon, Orthopaedic Department Russian Federation

M. Yu. Shchupak

Moscow City Cancer Hospital No 62; 27 poselok Istra, p/o Stepanovskoe, Krasnogorskiy rayon, Moskovskaya oblast', 143423, Russian Federation

Email: docbabkina@rambler.ru
MD, Orthopaedic Surgeon, Head of Orthopaedic Department Russian Federation

I. N. Kuznetsov

Moscow State University of Medicine and Dentistry named after A.I. Evdokimov; 20–1 Delegatskaya ul., Moscow, 127473, Russian Federation

Email: docbabkina@rambler.ru
PhD (in Biology), Research Assistant, Chair of Clinical Biochemistry and Laboratory Diagnostics, Faculty of Additional Professional Education Russian Federation

I. V. Boulytcheva

N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: docbabkina@rambler.ru
MD, PhD, Surgical Pathologist, Pathology Department Russian Federation

Yu. N. Solov'ev

N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: docbabkina@rambler.ru
MD, PhD, Professor, Member of Russian Academy of Sciences, Chief Research Fellow, Pathology Department Russian Federation

M. D. Aliev

N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: docbabkina@rambler.ru
MD, PhD, Professor, Member of Russian Academy of Sciences, Chief of Department of General Oncology Russian Federation

N. E. Kushlinskii

N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: docbabkina@rambler.ru
MD, PhD, Professor, Member-Correspondent of Russian Academy of Sciences, Head of Clinical Biochemistry Laboratory Russian Federation

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Copyright (c) 2016 Babkina I.V., Alferov A.A., Bondarev A.V., Shchupak M.Y., Kuznetsov I.N., Boulytcheva I.V., Solov'ev Y.N., Aliev M.D., Kushlinskii N.E.

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