Insuline-like growth factor 2 in paediatric gliomas: expression, intracellular localization and association with clinical outcome

FLORENCIA CLÉMENT; AYELEN MARTIN ; MARCELA VENARA; MARÍA CELIA FERNÁNDEZ; MERCEDES GARCÍA LOMBARDI ; IGNACIO BERGADÁ; PATRICIA PENNISI

Congreso; 58th Annual Meeting for the European Society for Paediatric Endocrinology; 2019

Background and Aim: Gliomas are the most frequent solidtumors in pediatric population. The IGF system of ligands andreceptors are known to play an important role in both normaland neoplastic growth. In a previous work we have reported thequantitation of some components of the IGFs system in SNCpediatric tumours (IGF-1, IGF-2, IGF-1R, IR), being IGF-2expression the most variable among all the genes studied.Our aim was to characterize the expression and intracellularlocalization of IGF-2 in pediatric gliomas, and its association withclinical outcome.Methods: We performed a prospective study (6/2012-01/2017)of pediatric patients with gliomas without previous medicaltreatment that underwent surgery in our Hospital. Tissues werecollected at the time of surgery. IGF-2 intracellular localizationwas assessed by Immunohistochemistry in fixed tumor samplesand gene expression was measured by qPCR in those where freshsample were available. IHC for IGF-2 was classified as negative orpositive, cytoplasmatic or cytoplasmatic/nuclear staining. Followup was carried out in collaboration with the Oncology service.Patients were categorized by their clinical outcome as dead, alivewith or without tumor. Mann-Whitney, Kruskal-Wallis followedby Dunn´s Test were used for comparisons.Results: We performed IHC for IGF-2 in 96 samples frompediatric gliomas (low grade n=80 and high-grade n=16) andfound IGF-2 negative staining in 10 samples, 19 samples withcytoplasmatic and 67 samples with cytoplasmatic and nuclearstaining. No association was found between IGF-2 cellularlocalization and tumor grade, nor with clinical outcome.Fresh samples from 34 patients with low (n= 27) and high(n= 7) grade gliomas, 15 M/ 19 F, and a median age of 7.41 years(range 0.96 ? 14.65) were processed for IGF-2 gene expressionquantitation. IGF-2 mRNA levels were detected in all samplesstudied. When analyzed by follow up (median 5.34 years; range2.35 ? 6.84), IGF-2 expression was higher in living patients bearingtumors compared to tumor free or deceased patients, regardless oftumor grade. This association persisted in low grade tumors whilewas not found in patient with high grade gliomas.