Low-molecular-weight fibroblast growth factor-2 — a viable prognostic factor for gastric gastrointestinal stromal tumors

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Abstract

Aim. To examine the expression of fibroblast growth factor-2 and its isoforms in gastrointestinal stromal tumors and assess the prognostic value of this marker.

Methods. The study included 44 patients with gastric gastrointestinal stromal tumors of the stomach who were prescribed surgical or combined treatment with the targeted drug imatinib (imatinib mesylate). Immunohistochemistry (IHC)-staining and immunoblotting with monoclonal antibodies were used to assess the expression of FGF-2. Statistical analysis for differences in clinical and morphological parameters was performed by using Student’s, Mann–Whitney–Wilcoxon and Fisher’s tests. Differences were considered significant at p < 0.05.

Results. Fibroblast growth factor-2 expression was assessed in tumor tissues in 39 out of 44 analyzed patients. The frequency of fibroblast growth factor-2 expression in the observed patients was 84.6% (33/39). The moderate and strong fibroblast growth factor-2 expression was detected in 21 (53.8%) patients with gastric gastrointestinal stromal tumors. High expression of low-molecular weight (18 kDa) fibroblast growth factor-2 isoform was found in all tumor samples from patients with high-risk gastrointestinal stromal tumor (prognostic group 6) (p=0.039), which indicated the active secretion of this ligand by its signalling pathway in the cancer cells. Patients with high levels of low‐molecular‐weight fibroblast growth factor-2 showed a higher level of Ki-67 proliferative activity (р=0.013) and tumor size (р=0.0017). Patients with increased expression of the low molecular weight isoform of fibroblast growth factor-2 in gastric gastrointestinal stromal tumor had a higher risk of recurrence, as well as larger tumor size and proliferative activity compared with patients without expression of this isoform. The level of fibroblast growth factor-2 expression in tumor samples, determined by immunohistochemistry-staining, increases after initiation of imatinib to based therapy, which may indicate the formation of resistance to this targeted drug and the progression of the disease.

Conclusion. The results of the study suggest that FGF-2 might be an independent prognostic marker of gastric gastrointestinal stromal tumor and a viable therapeutic target.

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About the authors

E G Mikheeva

Kazan State Medical University

Email: boichuksergei@mail.ru
Russian Federation, Kazan, Russia

A M Aukhadieva

Kazan State Medical University

Email: boichuksergei@mail.ru
Russian Federation, Kazan, Russia

A G Sabirov

Tatarstan Regional Clinical Cancer Center

Email: boichuksergei@mail.ru
Russian Federation, Kazan, Russia

S V Boichuk

Kazan State Medical University

Author for correspondence.
Email: boichuksergei@mail.ru
Russian Federation, Kazan, Russia

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2. Рис. 1. Экспрессия фактора роста фибробластов-2 в гастроинтестинальных стромальных опухолях (иммуногистохимическое окрашивание): негативная реакция (А); мембранная реакция (В); ядерная реакция умеренной интенсивности (С); яркая ядерная реакция (D)

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3. Рис. 2. Уровень экспрессии изоформ фактора роста фибробластов (FGF-2) (18, 22, 22,5 и 34 кДа) в гастроинтестинальных стромальных опухолях желудка, определяемый методом иммуноблоттинга. Образцы опухолей с высоким ­риском рецидивирования (группа риска 6) выделены пунктирной линией

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4. Рис. 3. A — уровень низкомолекулярной (18 кДа) изоформы фактора роста фибробластов-2 (FGF-2) у пациентов 5-й и 6-й прогностических групп (высокий риск рецидива) и пациентов 2-й и 3-й прогностических групп (низкий риск рецидива), p=0,039 (точный критерий Фишера). B, C — сравнение размеров (p=0,002, критерий Манна–Уитни) и индекса пролиферативной активности (p=0,013, критерий Манна–Уитни) в группах пациентов с гастроинтестинальными стромальными опухолями желудка, положительных и отрицательных по низкомолекулярной (18 кДа) изоформе FGF-2, согласно результатам иммуноблоттинга. Данные представлены медианой и квартильным размахом

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© 2021 Mikheeva E.G., Aukhadieva A.M., Sabirov A.G., Boichuk S.V.

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