Insulin Like Growth Factor (IGF) Systems Components in Pediatric Tumors of Central Nervous System (CNS): Association with clinical outcome. A key role for IGF-2??

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

Washington

Congreso; 10th International Meeting of Pediatric Endocrinology.; 2017

SLEP, LWPES, PES, ESPE

ObjectivesCNS tumors are the most frequent solid tumors in pediatric population. The IGFsystem of ligands and receptors are known to play an important role in both normaland neoplastic growth. Quantitation of components of this system have beenreported in adult CNS tumors, but information from pediatric patients is scarce. Our aim was to characterize the expression of IGF-1, IGF-1R, IGF-2 and IR in pediatric CNS tumors and its association with clinical outcome.MethodsWe performed a prospective study (6/2012-12/2016) of pediatric patients with CNStumors without previous medical treatment that underwent surgery in our Hospital.Tissues were collected at the time of surgery. Gene expression was measured by qPCR. Specimens were classified based on WHO2007 classification. Patients werecategorized by clinical outcome as dead, alive with or without tumor (follow up 2.24±1.36yr). Mann-Whitney, Kruskal-Wallis followed by Dunn´s Test were used for comparisons.ResultsWe included 104 patients (57 M/47 F), median age 8.5yr, (range 0.8-18.6). Themost common subgroups of CNS tumors were gliomas (n:43); ependymomas(n:21); medulloblastomas (n:13). We detected mRNA levels of the genes studied inall samples being IGF-2 the most variable. In gliomas, IGF-2 mRNA was lowerwhile IGF-1 expression was higher in high compared to low grade tumors. Whenanalyzed by follow up, IGF-2 and IR were increased in living patients with tumors respect to tumor free group. In ependymomas, IGF-2 and IR were lower in grade II & III compared to grade I tumors. IGF-1R expression differed between living patients carrying or not tumor. No differences were found in IGF-1, IGF-1R, IGF-2 and IR between classic and anaplastic medulloblastomas. However, an increase in the expression of all genes was found in living patients bearing tumors, with a mean follow up of 1.8yr.ConclusionsIGF-2 was the most variable gene of the IGF system. In gliomas and ependymomas IGF-2 was higher in lower grade tumors and IGF-2/IR circuit prevailed in living patients carrying tumors suggesting a role in their biological behavior. Initial elevated IGF-2 expression levels may be usefull as prognosis marker for clinical outcome in low grade gliomas.