LAUSR

Anaplastic lymphoma kinase (ALK) point mutations (within the kinase domain), gene amplification and protein overexpression are identified (8-14%) both in familial and sporadic high-risk neuroblastoma (HR-NB). ALK mutations are much more frequent at time of relapse and were associated with poor clinical outcomes for children with HR-NB. Evidently, ALK is near exclusively co-amplified with MYCN, and the cooperative activity of ALK and MYCN are known to drive HR-NB pathogenesis. However, the ALK protein expression and its role in the prognosis of MYCN non-amplified NB remained unexplored. In this study, NB tumors representing varied stages, ages, sites, diagnosis/progressive disease, primary/metastatic site from a cohort MYCN non-amplified NB patients (n=92) were custom archived in TMAs and stained with ALK (immunohistochemistry) antibody. The correlations between ALK protein expression, and clinico-pathological and biological variables of MYCN non-amplified NB tumors were analyzed. Assessing the strong positivity, high expression of ALK protein could be detected in 47 (51%) of the 92 NB tumors. The majority of NBs with evident of ALK protein high expression exhibited undifferentiated or poorly differentiated histology (39/47, 82.9%). ALK protein high expression significantly predicted worse survival outcomes for NB (and HR-NB subset) patients with MYCN non-amplified status. Transcriptional data mining (R2: Genomics Analysis and Visualization Platform) across multiple cohorts of MYCN non-amplified NB patients revealed unique and defined associations of ALK to the adverse clinical prognostic factors (e.g. advanced disease stage, risk) and poor survival outcomes. Our study recognized the prognostic role of ALK protein expression in MYCN non-amplified NB. Since, ALK is indicated to transactivate MYCN, increase MYCN protein expression, and coordinate disease progression; further studies are warranted to define the mechanism(s) of ALK high-expression associated disease evolution in MYCN non-amplified HR-NB.Funding: This work was partially or in full, funded by Oklahoma Center for the Advancement of Science and Technology, OCAST-HR19-04; National Institutes of Health, NIH-P20GM103639 and; NIH-NCI- Cancer Center Support Grant P30CA225520 Citation Format: Natarajan Aravindan, Dinesh Babu Somasundaram, Santny Shanmugarama, Sheeja Aravindan. ALK protein expression and its prognostic significance in MYCN non amplified neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3036.