Components of the Insulin-Like Growth Factor (IGF) System in Paediatric Gliomas Upon Diagnosis According to WHO 2007 Grading

CLÉMENT, FLORENCIA; MARTIN, AYELÉN; VENARA, MARCELA; MAGLIO, SILVANA; MATHÓ, CECILIA; GARCÍA LOMBARDI, MERCEDES; BERGADÁ, IGNACIO; PENNISI, PATRICIA

Puerto Varas

Congreso; XXV Reunión Anual de la Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP); 2015

Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)

Background: Gliomas are the most common central nervous system tumours in children. Histologic grading is a means of predicting the biological behavior of these tumours and survival is strongly correlated with tumour gradation. The insulin-like growth factor (IGF) system of ligands and receptors are known to play an important role in both normal and neoplastic cellular growth. Information about the association of IGF-1, IGF-2, Insulin Receptor (IR) isoforms and IGF-1 receptor intracellular localization with tumour grading in paediatric gliomas is lacking. Objective: To perform a quantitative assessment of IGF system components and to characterize intracellular localization of the IGF-IR in glial tumours from paediatric patients according to WHO 2007 grading. Patients and Methods: In this prospective study we included 37 patients (20 males, age range 0.87?18.2), with gliomas without previous medical treatment. Total RNA was extracted from frozen tumour samples and IGF-1, IGF-2, IGF-1R and IR expression was quantified by qPCR. IR isoforms were assessed by PCR. Formalinfixed tumour tissue sections were immunostained for IGF-1Rβ. IGF-1R expression and intracellular localization were scored as positive, negative, nuclear or cytoplasmic. Contingency tables were analyzed using Pearson?s χ2 test to assess relationships between IGF-1R and tumor grade (Low grade I-II; High grade IIIIV). Results: IGF-1R staining was positive in 25/30 (83.3%) low grade and in 7/7 (100%) high grade gliomas. Low grade tumours showed cytoplasmic localization of IGF-1R in 22/25 cases, while in high grade tumours IGF-1R localization was mainly nuclear (5/7) (p < 0.05). No differences were found between groups in total IR or IGF-1R. IR isoform A was present and predominant in all gliomas. IGF-1 expression was higher in high grade tumours, while IGF-2 expression was higher in low grade tumours (p < 0.05, Mann Whitney Test). Conclusions: Our results would indicate that the amount of IGF-1R and IR expression are similar in all gliomas. However, IGF-2/IR components seems to have a role in low grade gliomas while IGF-1R intracellular localization and IGF-1 expression are associated with high grade gliomas, suggesting that an intratumoral IGF1/IGF-1R circuit may be involved in the biological behavior of this particular type of paediatric tumours.