| Project/Area Number |
16591424
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
MITSUDOMI Tetsuya Aichi Cancer Center Res.Inst., Molecular Oncology, Researcher, 分子腫瘍学部, 研究員 (70209807)
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| Co-Investigator(Kenkyū-buntansha) |
YATABE Yasushi Aichi Cancer Center Res.Inst., MOlecular Oncology, Researcher, 分子腫瘍学部, 研究員 (90280809)
TAKAHASHI Takashi Nagoya University Graduate School of Medicine, Division of Molecular Oncology, Center for Neurological disease and Cancer, Professor, 大学院・神経疾患腫瘍分子医学研究センター・腫瘍病態制御部門, 教授 (50231395)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | lung cancer / EGFR / K-ras / p53 / prognostic factor / predictive factor / number of metastatic lymph nodes / database / PIK3CA / PTEN / 上皮成長因子受容体(EGFR) / 腺癌 / K-ras遺伝子 / p53遺伝子 / 非喫煙者肺癌 |
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| Research Abstract |
Just after the initiation of this project, mutations of the gene for epidermal growth factor receptor (EGFR) were discovered. Accordingly, our main efforts were made on mutational analyses of the EGFR, K-ras, p53 and PIKsCA gene and their clinical implications.
EGFR were present in 111 (40%) in 277 lung cancer cases. Exon 19 deletion (47%) and point mutation at codon 858 in exon 21 (44%) accounted for more than 90% of the mutations. EGFR mutations were siginificantly more frequent in women than men, in non-smokers than ever-smokers, and in adenocarcinoma than non-adenocarcinoma (all P<0.001). EGFR mutations and K-ras mutations had mutually exclusionary relationship, however, p53 mutations occurred independently of the EGFR mutations.
In 59 patients who received gefitinib for their recurrent disease, EGFR mutations were present in 33. Response to gefitinib was observed in 83% of the patients with EGFR mutations and in 10 of those without EGFR mutation. Patients with EGFR mutations survived for a significantly longer period. In this cohort, K-ras mutations were found in 9 and none of these patients responded to gefitinib. Survival was shorter in this group of patients. Two patients had PIK3CA mutation as well as EGFR mutation.
To further develop clinical database, we also evaluated effects of number of metastatic lymph nodes on patient survival. Number of metstatic node proved to be useful predictor of prognosis and may add further information to the current TNM staging system.
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