ESPE Abstracts (2019) 92 P1-359

Insulin-Like Growth Factor 2 in Pediatric Gliomas: Expression, Intracellular Localization and Association with Clinical Outcome

Florencia Clément1, Ayelen Martin1, Marcela Venara1, María Celia Fernández1, Mercedes García Lombardi2, Ignacio Bergadá1, Patricia Pennisi1

1Centro de Investigaciones Endocrinológicas "Dr. César Bergadá",(CEDIE) CONICET – FEI – División de Endocrinología, Hospital de Niños "Ricardo Gutiérrez", Buenos Aires, Argentina. 2Servicio de Oncología, Hospital de Niños "Dr. Ricardo Gutiérrez", Buenos Aires, Argentina

Background and Aim: Gliomas are the most frequent solid tumors in pediatric population. The IGF system of ligands and receptors are known to play an important role in both normal and neoplastic growth. In a previous work we have reported the quantitation of some components of the IGFs system in SNC pediatric tumours (IGF-1, IGF-2, IGF-1R, IR), being IGF-2 expression the most variable among all the genes studied.

Our aim was to characterize the expression and intracellular localization of IGF-2 in pediatric gliomas, and its association with clinical outcome.

Methods: We performed a prospective study (6/2012-01/2017) of pediatric patients with gliomas without previous medical treatment that underwent surgery in our Hospital. Tissues were collected at the time of surgery. IGF-2 intracellular localization was assessed by Immunohistochemistry in fixed tumor samples and gene expression was measured by qPCR in those where fresh sample were available. IHC for IGF-2 was classified as negative or positive, cytoplasmatic or cytoplasmatic/nuclear staining. Follow up was carried out in collaboration with the Oncology service. Patients were categorized by their clinical outcome as dead, alive with or without tumor. Mann-Whitney, Kruskal-Wallis followed by Dunn´s Test were used for comparisons.

Results: We performed IHC for IGF-2 in 96 samples from pediatric gliomas (low grade n=80 and high-grade n=16) and found IGF-2 negative staining in 10 samples, 19 samples with cytoplasmatic and 67 samples with cytoplasmatic and nuclear staining. No association was found between IGF-2 cellular localization 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 expression quantitation. IGF-2 mRNA levels were detected in all samples studied. When analyzed by follow up (median 5.34 years; range 2.35 – 6.84), IGF-2 expression was higher in living patients bearing tumors compared to tumor free or deceased patients, regardless of tumor grade. This association persisted in low grade tumors while was not found in patient with high grade gliomas.

Conclusions: In contrast with results found in other tumors, IGF-2 intracelular localization performed by IHC does not correlate with clinical outcome in pediatric gliomas. In low grade gliomas the association of initial elevated IGF-2 mRNA levels with clinical outcome suggest a role for IGF2 in the biological behavior of these tumors and could be a valuable prognosis marker.

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