Abstract 707: Evaluating HER4 as a potential driver of disparities in Hispanics with pediatric osteosarcoma

Abstract Osteosarcoma (OS) is the most common primary malignant bone tumor in children, with a particularly high incidence and high rates of metastatic disease in Hispanic and African American patients. With the goal of understanding disparities within underrepresented communities affected by pediatric OS, we recently described the epidemiology of pediatric OS within a Hispanic patient cohort. We demonstrated that malignant bone tumors represent 4.68% of all pediatric cancers in Hispanics living in Puerto Rico, with an age-adjusted incidence of 6.02 cases per million. Notably, 34.62% of these patients present localized disease while 42.3% have metastatic disease at diagnosis with a mortality rate of 2.4 per million. These statistics highlight the need for dedicated studies to address clinical and biological causes for disparities in underserved populations. The Human Epidermal Growth Factor Receptor 4 (HER4), a member of the EGFR receptor tyrosine kinase family, has been demonstrated to be upregulated in pediatric OS patients leading to decreased overall survival. This receptor regulates pathways responsible for cell survival, proliferation, and differentiation and has been implicated in tumorigenesis in various cancers. Furthermore, the EGFR family can also modulate immune cell populations, although this is largely understudied in HER4 positive tumors including aggressive pediatric osteosarcoma. The goal of our study is to evaluate HER4 expression in a cohort of Hispanic patients with pediatric osteosarcoma and determine whether HER4 expression can be predetermined by genetic ancestry. We hypothesize that underrepresented minorities including Hispanics and African Americans have higher HER4 expression, predisposing these patients to aggressive OS. By retrospective medical record review between 2009-2023, we identified 45 patients between the ages of 1-19 years diagnosed with pediatric OS. Thirty-one pediatric OS tissue blocks were deemed adequate for further studies, including biopsies, metastases, resections, and relapses from the Pathology Department of the Puerto Rico Medical Center. We performed immunohistochemistry (IHC) for HER4 expression using a validated monoclonal HER4 antibody (Invitrogen). Our results show high HER-4 expression in the majority of our Hispanic patient cohort with pediatric OS, suggesting that HER4 may play drive a crucial step in OS tumor progression and metastasis within these communities. Ongoing analysis includes evaluating HER4 expression within other ethnic groups including Hispanics in US, Caucasians, and African Americans. Furthermore, we are also evaluating the immune cell compartment in HER4+ pediatric OS by single cell sequencing and spatial transcriptomics. Understanding how genetic ancestry can lead to disparities in pediatric OS has the potential to result in effective targeted therapeutic strategies for underserved minorities. Citation Format: Rocio Krystal Rivera-Valentin, Carolyn M. Ruiz-Perez. Evaluating HER4 as a potential driver of disparities in Hispanics with pediatric osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 707.