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

CLEMENT FLORENCIA; MARTIN AYELEN; VENARA MARCELA; MAGLIO SILVANA; GARCÍA LOMBARDI MERCEDES; BERGADÁ IGNACIO; PENNISI PATRICIA A

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

Sociedad Latinoamericana de Endocrinología Pediatrica

Background: Gliomas are the most common central nervoussystem tumours in children. Histologic grading is a means of predictingthe biological behavior of these tumours and survival isstrongly correlated with tumour gradation. The insulin-likegrowth factor (IGF) system of ligands and receptors are known toplay an important role in both normal and neoplastic cellulargrowth. Information about the association of IGF-1, IGF-2, InsulinReceptor (IR) isoforms and IGF-1 receptor intracellular localizationwith tumour grading in paediatric gliomas is lacking.Objective: To perform a quantitative assessment of IGF systemcomponents and to characterize intracellular localization of theIGF-IR in glial tumours from paediatric patients according toWHO 2007 grading.Patients and Methods: In this prospective study we included37 patients (20 males, age range 0.87?18.2), with gliomas withoutprevious medical treatment. Total RNA was extracted from frozentumour samples and IGF-1, IGF-2, IGF-1R and IR expression wasquantified by qPCR. IR isoforms were assessed by PCR. Formalinfixedtumour tissue sections were immunostained for IGF-1Rβ.IGF-1R expression and intracellular localization were scored aspositive, negative, nuclear or cytoplasmic. Contingency tableswere analyzed using Pearson?s χ2 test to assess relationships betweenIGF-1R and tumor grade (Low grade I-II; High grade IIIIV).Results: IGF-1R staining was positive in 25/30 (83.3%) lowgrade and in 7/7 (100%) high grade gliomas. Low grade tumoursshowed cytoplasmic localization of IGF-1R in 22/25 cases, while inhigh grade tumours IGF-1R localization was mainly nuclear (5/7)(p < 0.05). No differences were found between groups in total IRor IGF-1R. IR isoform A was present and predominant in all gliomas.IGF-1 expression was higher in high grade tumours, whileIGF-2 expression was higher in low grade tumours (p < 0.05, MannWhitney Test).Conclusions: Our results would indicate that the amount ofIGF-1R and IR expression are similar in all gliomas. However,IGF-2/IR components seems to have a role in low grade gliomaswhile IGF-1R intracellular localization and IGF-1 expression areassociated with high grade gliomas, suggesting that an intratumoralIGF1/IGF-1R circuit may be involved in the biological behaviorof this particular type of paediatric tumours.