Characterization of Insulin Like Growth Factor (IGF) System Components in Pediatric Tumors of Central Nervous System (CNS)

MARTIN, A.; CLÉMENT, F.; VENARA, M.; MAGLIO, S.; MATHO, C.; GARCÍA LOMBARDI, M.; BERGADÁ, I.; PENNISI, P.

Buenos Aires

Congreso; XXVI Reunion Anual de la Sociedad Latinoamericana de Endocrinología Pediatrica; 2016

Background: CNS tumors are the most frequent solid tumorsin pediatric population. The IGF system of ligands and receptorsare known to play an important role in both normal and neoplasticgrowth. Recently, quantitation of components of this systemhave been reported in CNS tumors from adult population, but informationfrom pediatric patients is scarce.Objective: To characterize the expression of IGF-1, IGF-1R,IGF-2 and IR in CNS tumors from pediatric patients.Patients and Methods: We performed a prospective study(6/2012?6/2016) of pediatric patients with CNS tumors withoutprevious medical treatment that underwent surgery in our Hospital.Tissues were collected at the time of surgery. IGF-1, IGF-1R,IGF-2 and IR expression was measured by qRTPCR using extractedRNA. Specimens were classified according to localization orhistology type and grade based on WHO2007 classification. Mann-Whitney, Kruskal-Wallis followed by Dunn?s Testwere used forcomparisons.Results: We included 89 patients (50 males/39 females), medianaged 8.9!yrs, (range 0.9?18.6). The most common subgroupsof CNS tumors were gliomas (n:36); ependymomas (n:16); medulloblastomas(n:11). Levels of IGF-1, IGF-1R, IGF-2 and IR mRNAwere detectable in all specimens. Changes in IGF-2 mRNA levelsamong tumors were significantly different compared to the changesobserved in the other genes analyzed (IGF-2:47 (12?82) vs. IGF-1:1 (0.7?1.4); IGF-1R:0.8 (0.5?1.0); IR: 0.9 (0.7?1.1), mean (CI)fold change, p!< 0.0001). In gliomas IGF-2 mRNA was lower whileIGF-1 expression was higher in high grade compared to low gradetumors (p!< 0.05). IGF-IR and IR mRNAs were similar. Expressionof IGF-2 and IR were lower in grade 2 and 3 ependymomas comparedto grade 1, while IGF-1 and IGF-1R were similar amonggrades. When analyzed according to localization (supra/infratentorial,spinal cord) we found that IGF-1R expression was low insupratentorial ependymomas (p!< 0.001). Finally, we found no differencesin IGF-1, IGF-1R, IGF-2 and IR expression levels betweenclassic and anaplastic medulloblastomas.Conclusions: IGF-2 is highly variable in pediatric CNS tumorscompared to other components of the IGF system. In gliomas andependymomas IGF-2 was higher in lower grade tumors suggestinga role for IGF-2 in their biological behaviour. Further studies includingpatients? follow up are necessary to confirm these results.