Histological markers, sickle-shaped blood vessels, myxoid area, and infiltrating growth pattern help stratify the prognosis of patients with myxofibrosarcoma/undifferentiated sarcoma

Myxofibrosarcoma (MFS) and undifferentiated sarcoma (US) have been considered as tumors of the same lineage based on genetic/epigenetic profiling. Although MFS shows a notably better prognosis than US, there are no clear criteria for distinguishing between them. Here, we examined 85 patients with MFS/US and found that tumors with infiltrative growth patterns tended to have more myxoid areas and higher local recurrence rates but fewer distant metastases and better overall survival. Morphologically characteristic sickle-shaped blood vessels, which tended to have fewer alpha SMA-positive cells, were also observed in these tumors, compared with normal vessels. Based on the incidence of these sickle-shaped blood vessels, we subdivided conventionally diagnosed US into two groups. This stratification was significantly correlated with metastasis and prognosis. RNA sequencing of 24 tumors (9 MFS and 15 US tumors) demonstrated that the proteasome, NF-kB, and VEGF pathways were differentially regulated among these tumors. Expression levels of KDR and NFATC4, which encode a transcription factor responsible for the neuritin-insulin receptor angiogenic signaling, were elevated in the sickle-shaped blood vessel-rich US tumors. These findings indicate that further analyses may help elucidate the malignant potential of MFS/US tumors as well as the development of therapeutic strategies for such tumors.

Automated summary

Based on a study of 85 patients with MFS/US, it was found that tumors with infiltrative growth patterns tended to have more myxoid areas and higher local recurrence rates, but fewer distant metastases and better overall survival. Sickle-shaped blood vessels were observed in these tumors, which were characterized by fewer alpha SMA-positive cells compared with normal vessels. By classifying conventionally diagnosed US tumors based on the incidence of these sickle-shaped blood vessels, a significant correlation was found with metastasis and prognosis. RNA sequencing revealed differential regulation of the proteasome, NF-kB, and VEGF pathways in MFS/US tumors, providing potential targets for therapeutic strategies.