Pathological and molecular study of lung pleomorphic carcinomas to clarify the pathogenesis and develop novel treatment strategy

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10699
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Keio University
• Principal Investigator: Hishida Tomoyuki 慶應義塾大学, 医学部(信濃町), 准教授 (40544664)
• Research Collaborator: KURIYAMA Shoji ; NAKAGOMI Takahiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 呼吸器外科学 / 病理学

Outline of Final Research Achievements

We performed clinicopathological and molecular study to clarify pathogenesis of lung cancer with sarcomatous component (LCSC) including pleomorphic carcinoma, which has high-grade malignancy. We reviewed our medical record and identified 23 patients who underwent resection for LCSC from 1996 to 2011. The 5-year recurrence-free survival was 56%, and 8 (35%) patients developed recurrence. Among them, 7 had recurrence within 1 year after surgery, and median post-recurrence survival was only 3 months. On the other hand, 5-year recurrence-free survivors were found in 6 (26%) patients, which suggested that LCSC might have 2 groups in terms of biological behavior; the poor outcome group as shown in previous studies and the favorable outcome group. Next, we conducted molecular analysis to clarify biological signatures in sarcomatous component, a characteristic component associating with malignant behavior of LCSC, comparing with non-sarcomatous component and non-cancerous area of each case.

Free Research Field

呼吸器外科学

Academic Significance and Societal Importance of the Research Achievements

多形癌に代表される「肉腫様成分を含む肺癌」は、原発性肺癌の中でも増殖が速く、他臓器やリンパ節に転移しやすい悪性度が高い腫瘍である。完全切除されても、術後再発は高頻度であり、また、現状の化学療法や放射線療法には抵抗性で、肺腺癌におけるEGFR遺伝子変異やALK融合遺伝子などの有効な治療標的も同定されていない。本研究は、難治癌である「肉腫様成分を含む肺癌」の新規治療開発の足がかりとなる基盤を構築するものであり学術的かつ社会的意義は非常に大きい。