Minimal Disseminated Disease Evaluation in Paediatric Ewing Sarcoma Patients

Ewing sarcoma (EwS) is the second most common paediatric bone tumour, driven by chromosomal translocations, primarily t(11;22) and t(21;22), involving EWSR1, FLI1, and ERG genes. Metastases at diagnosis are the most significant prognostic factor and PET-CT imaging is considered the gold standard for detecting bone marrow (BM) metastases. The evaluation of Minimal Disseminated Disease (MDD), which reflects tumour cells present in BM at diagnosis, could offer a more sensitive method to identify micro-metastases, though its prognostic value remains debated. This study aims to define a transcript panel, including EwS fusion and overexpressed transcripts, to detect MDD in BM and to correlate the results with patient prognosis. Overexpressed transcripts are identified through a bioinformatic analysis and validated by quantitative PCR and four candidates (CAV1, TWIST1, CAV2, GLCE) are selected to be included in the panel. A EwS patient cohort is tested for MDD with the transcript panel and the results are correlated with prognosis, exploiting Kaplan-Meier curves. EwS fusion transcripts in BM are found to be prognostic, particularly for localized EwS patients. Positivity for the panel result prognostic as well. Specifically considering positivity to CAV1, CAV2, and GLCE and negativity to EwS fusion transcripts, the results provide an implemented patient stratification.