311P Differences in stromal component of chordoma are associated with contrast enhancement in MRI and differential gene expression in RNA sequencing

Abstract

A recent study suggested that stroma percentage may have an important clinical impact on chordoma as it may be associated with tumor progression and treatment response. Considering that radiologic features, such as contrast enhancement and T2 signal intensity, are closely related with tumor component, we hypothesized that stroma and tumor cell component in chordomas may be associated with radiologic features visible on MRI and further associated with different histopathological features and genetic expressions. Therefore, we aimed to investigate whether chordomas with different stroma component show radiologic and genetic differences to obtain a better understanding of the heterogeneity of the disease. A total of 45 patients diagnosed with chordoma were selected between May 2011 and March 2020 from a single institute. Electronic medical records, pathology slides, and pretreatment magnetic resonance imaging (MRI) scans were reviewed. Of the 45 patients, 10 (4 stroma-rich and 6 stroma-poor chordomas) were further analyzed using RNA sequencing. Differential gene expression and gene set analysis were performed. There were 25 (55.6%) stroma-rich and 20 (44.4%) stroma-poor chordomas. No clinical differences were found between the two groups. Radiologically, stroma-rich chordomas showed significant signal enhancement on MRI. Based on the results of RNA sequencing, the upregulated genes in stroma-rich chordomas were cartilage-, collagen/extracellular matrix-, and tumor metastasis/progression-associated genes. Contrarily, tumor suppressor genes were downregulated in stroma-rich chordomas. In conclusion, the stromal component of chordoma differentially affects radiologic features and defines different genetic subgroups of chordoma. However, additional investigations with a larger cohort are needed to verify its clinical significance.