Molecular biological analysis and differential diagnosis of undifferentiated sarcoma and myxofibrosarcoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16210
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kanagawa Cancer Center Research Institute
• Principal Investigator: washimi kota 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, 医師 (30716733)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 未分化肉腫 / 粘液線維肉腫 / 鎌状血管

Outline of Final Research Achievements

We examined 85 patients with myxofibrosarcoma (MFS)/undifferentiated sarcoma (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 αSMA‐ 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 demonstrated that the proteasome, NF‐kB, and VEGF pathways were differentially regulated among these tumors. Elucidating the mechanisms of sickle-shaped blood vessels could help identify factors involved in distant metastasis and develop therapeutic strategies.

Free Research Field

骨軟部腫瘍

Academic Significance and Societal Importance of the Research Achievements

未分化肉腫に関しては、診断根拠や予後について不明な点が多い。未分化肉腫は血行性の遠隔転移が重要な予後不良因子であり、血行性転移の予測は重要である。本研究から未分化肉腫に関して、鎌状血管が多く見られる症例では有意に血行性転移が多い傾向が見られ、鎌状血管形成が目立つ症例ではNF-kB、VEGF経路の遺伝子変異が関与している可能性が示唆された。この鎌状血管形成機序を解明することで、未分化肉腫の血行性転移に関わる因子の解明につながる可能性があり、未分化肉腫の予後予測因子として利用するだけでなく、治療戦略に役立つ可能性があると考える。