Lung fibrosis caused by Gefitinib therapy for lung cancer with EGFR mutation

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590438
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Japanese Foundation for Cancer Research (2013-2014); National Defense Medical College (2012)
• Principal Investigator: MATSUBARA Osamu 公益財団法人がん研究会, その他部局等, 研究員 (40107248)
• Co-Investigator(Kenkyū-buntansha): ISHIKAWA Yuichi がん研究所, 病理部, 部長 (80222975)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肺線維症 / 間質性肺炎 / 病理発生機序 / EGFR変異肺癌

Outline of Final Research Achievements

Gefitinib therapy is very effective for lung cancer with epithelial growth factor receptor (EGFR) mutation, but it sometimes causes interstitial pneumonia/lung fibrosis. The important pathohistology shows destruction of alveolar structures, activation of fibroblastic foci and an increase of myofibroblasts. We studied pathological materials of video-assisted thoracoscopic surgery (VATS) lung biopsy, using 20 cases including 5 Gefitinib therapy cases and 10 controls to examine molecular mechanism of activation.　Immunohistochemically myofobroblasts were positive for a-SMA, vimentin, desmin　and regenerated pneumocytes were positive for TGF-b and CTGF. Pneumocytes revealed apoptosis. Myofibroblasts are thought to appear by epithelial mesenchymal transformation (EMT). Proteome analysis showed the difference of protein expression of some proteins, such as annexin A3, plastin-2, Hsp 27 and Hsp 70. We now have examined again to confirm the results.

Free Research Field

人体病理学