Abstract LB-221: Aggresome-based classification is a promising prognostic marker for pediatric choroid plexus tumors

Abstract Protein misfolding and aggregation result in proteotoxic stress, and underlie the pathogenesis of many diseases. To overcome proteotoxicity, cells compartmentalize misfolded and aggregated proteins in different inclusion bodies. Aggresome is a paranuclear inclusion body that functions as a storage compartment for misfolded proteins. Our previous work revealed the presence of aggresomes in pediatric choroid plexus tumors (CPT). CPTs are rare neoplasms comprised of three pathological subgroups; choroid plexus carcinoma (CPC), a grade III tumor, atypical choroid plexus papilloma (ACPP), a grade II tumor, and choroid plexus papilloma (CPP), a grade I tumor. In the current study, we aimed to investigate the prognostic value of aggresomes-positivity and if it could be used to improve the disease subclassification. Forty two pediatric CPT tumor samples were stratified into two molecular subgroups; Cluster “A", and “B”, using Illumina Infinium Methylation EPIC BeadChip array. Kaplan Meier analysis showed that “cluster B” is associated with significantly shorter overall survival (OS) and event free survival (EFS) with P= 0.008 and P =0.007 respectively. Aggresomes were detected in 64.2% of samples using immunohistochemistry and they were distributed among different pathological and molecular subgroups. The presence of aggresomes significantly correlated with patient outcome in both OS (P = 0.057) and EFS (P = 0.051). The survival-based cutoff determination was performed using various percentages of aggresomes; ranging from 10% to 50%. Aggresome presence maintained significance at all cutoffs, yet the 25% cutoff had the highest impact in OS and EFS (P = 0.001). Moreover, the classification based on the 25% cutoff concurred with the methylation signature of low-risk “A” and high-risk “B” clusters. Hence, the detection of aggresomes in CPTs provides a new prognostic marker supporting histopathological tumor classification. Citation Format: Nada Amer, Hala Taha, Dina Hesham, Noura Mahmoud, Moatasem Elayadi, Amal Mossab, Ayda Youssef, Mohamed Elbeltagy, Mohamed Saad Zaghloul, Ahmad Abdel Azziz, Shahenda El-Naggar. Aggresome-based classification is a promising prognostic marker for pediatric choroid plexus tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-221.